ArticlePublisher preview availableLiterature Review

IL-17 inhibition: is it the long-awaited savior for alopecia areata?

Authors:
  • Giuliani, Milan, Italy
To read the full-text of this research, you can request a copy directly from the authors.

Abstract and Figures

Interleukin-17 (IL-17) has been implicated in the pathogenesis of a large number of inflammatory and autoimmune conditions, including skin disorders such as psoriasis. Recently, much data have accumulated on the possible role of IL-17 in the pathogenesis of alopecia areata (AA). In this review, the available information on the connection between AA and IL-17 is described. While IL-17 levels are consistently reported to be elevated in the serum and lesional skin of AA patients, there is no clear connection between IL-17 levels and disease severity or duration. Some evidence has suggested an association between IL-17 and an early-onset disease, although this awaits further confirmation. While there is enough information to support clinical trials with IL-17-targeted treatments, it is possible that they will be effective only in a subset of AA patients. Further studies are warranted to better delineate the exact role of IL-17 in AA pathogenesis.
This content is subject to copyright. Terms and conditions apply.
Vol.:(0123456789)
1 3
Archives of Dermatological Research (2018) 310:383–390
https://doi.org/10.1007/s00403-018-1823-y
REVIEW
IL-17 inhibition: isit thelong-awaited savior foralopecia areata?
YuvalRamot1· BarbaraMarzani2· DanielaPinto2· ElisabettaSorbellini3· FabioRinaldi3
Received: 11 July 2016 / Revised: 24 January 2018 / Accepted: 23 February 2018 / Published online: 1 March 2018
© Springer-Verlag GmbH Germany, part of Springer Nature 2018
Abstract
Interleukin-17 (IL-17) has been implicated in the pathogenesis of a large number of inflammatory and autoimmune condi-
tions, including skin disorders such as psoriasis. Recently, much data have accumulated on the possible role of IL-17 in the
pathogenesis of alopecia areata (AA). In this review, the available information on the connection between AA and IL-17 is
described. While IL-17 levels are consistently reported to be elevated in the serum and lesional skin of AA patients, there
is no clear connection between IL-17 levels and disease severity or duration. Some evidence has suggested an association
between IL-17 and an early-onset disease, although this awaits further confirmation. While there is enough information to
support clinical trials with IL-17-targeted treatments, it is possible that they will be effective only in a subset of AA patients.
Further studies are warranted to better delineate the exact role of IL-17 in AA pathogenesis.
Keywords Alopecia areata· IL-17· Autoimmunity· Hair· Secukinumab
Introduction
Interleukin-17 (IL-17) has gained much interest in recent
years, due to its main role in the pathogenesis of a large
number of inflammatory and autoimmune disorders. This
interest has been further fueled following the recent develop-
ment of specific inhibitors of this cytokine and its receptors,
which show very promising efficacy in several inflammatory
conditions, such as psoriasis and rheumatoid arthritis. The
dermatology field, which has been exposed to IL-17 mainly
due to the recent approval of IL-17 inhibitors for psoriasis,
has explored the potential benefit of these drugs in other
skin conditions, such as atopic dermatitis, hidradenitis sup-
purativa and cutaneous lupus [88]. Alopecia areata (AA)
is one of the skin conditions being explored as a potential
target for IL-17 inhibition, as data have accumulated on the
possible role of IL-17 and Th17 in its pathogenesis. Much
of these data have been published in the last 5years, and the
reported results depict a more or less clear picture on its role
in the pathological mechanism of the disease.
The aim of this manuscript is to provide a comprehensive
review on the role of IL-17 and Th17 in AA pathogenesis.
We start by providing information on the IL-17 pathway,
continue by exploring the reports which link IL-17 to AA,
and summarize by integrating the available information to
provide some leads to the possibility of treating AA with
IL-17-targeted therapies. This manuscript focuses on IL-17
and AA, and does not intend to provide a complete picture
of the different cytokine pathways that take part in AA
pathogenesis, as this is beyond the scope of this review, and
has been reviewed in detail in several recent papers [38, 96,
98]. However, some of the more important pathways that are
activated in AA will be reviewed briefly, to give the reader
a more comprehensive understanding on the complexity of
this condition.
The IL‑17 pathway
The IL-17 family of cytokines includes six members: IL-
17A, IL-17B, IL-17C, IL-17D, IL-17E/IL-25, and IL-17F.
IL-17 is produced by neutrophils, natural killer cells, CD8+
T cells and γδ T cells [23]. However, the major source for
IL-17 is the Th17 cells. These are a subset of CD4+ helper
T cells, which are induced to differentiate into Th17 cells by
transforming growth factor-β, IL-6, IL-1β, and tumor necro-
sis factor (TNF)-α, and their maintenance is supported by
* Yuval Ramot
yramot@gmail.com
1 Department ofDermatology, Hadassah–Hebrew University
Medical Center, PO Box12000, 9112001Jerusalem, Israel
2 Giuliani S.p.a., Milan, Italy
3 International Hair Research Foundation (IHRF), Milan, Italy
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
... It also affects the activation and migration of mainly neutrophils and the development of a rapid inflammatory response [20]. It plays a role in the etiopathogenesis of inflammatory and autoimmune diseases such as psoriasis, rheumatoid arthritis or Crohn's disease [21,22]. An increase in the IL-17 concentration as well as a higher concentration of Th17 cells also in the blood serum of AA patients have been demonstrated in the literature and potentially points to new therapeutic options using IL-17 inhibitors [20][21][22][23][24]. ...
... It plays a role in the etiopathogenesis of inflammatory and autoimmune diseases such as psoriasis, rheumatoid arthritis or Crohn's disease [21,22]. An increase in the IL-17 concentration as well as a higher concentration of Th17 cells also in the blood serum of AA patients have been demonstrated in the literature and potentially points to new therapeutic options using IL-17 inhibitors [20][21][22][23][24]. ...
Article
Full-text available
Introduction: Alopecia areata (AA) is one of the most common causes of non-scarring hair loss in adults and children with unknown etiopathogenesis, however immunological factors play an important role. Aim: To evaluate the concentration of interleukin (IL) 10 (IL-10), IL-12, IL-17 and IL-35 in the blood serum of patients with AA. Material and methods: AA study group consisted of 118 patients. The control group consisted of 54 healthy individuals. The severity of the disease was assessed by SALT score. In the study group, the percentage of hair loss averaged 49.6% ±36.3%. The concentration of IL-10, IL-12, IL-17 and IL-35 in the serum was assessed by the enzyme-linked immunosorbent assays (ELISA). Results: In patients with AA, the level of IL-12 and IL-17 was significantly higher than in the control group (p > 0.05). The level of IL-10 in patients was slightly higher, whereas the level of IL-35 was slightly lower, compared to the control group, but those differences were not statistically significant. Furthermore, in patients with more severe disease the IL-12 level was significantly higher as compared to patients with the less severe AA (p < 0.05). Conclusions: The etiopathogenesis of AA is complex, however Th1 and Th17 lymphocytes and their increased activity are undoubtedly significant contributors in this process. Disorders of immunological processes in AA require further research in order to understand the underlying pathomechanisms of the disease and to provide potential therapeutic strategies.
... Otras citoquinas que tienen un papel en la inmunopatología es la IL-23, que es proinflamatoria y promotora de autoinmunidad, al promover la diferenciación y proliferación de los linfocitos Th17 12 y se considera un factor clave para mantener constante la población Th17 13 . La IL-17 producida mayormente por linfocitos Th17 y en menor medida por neutrófilos, células NK y mastocitos 14 , se encarga de estimular a los linfocitos CD8+ para que produzcan TNF-α e IFN-γ, que contribuyen a la inflamación en el folículo piloso por una retroalimentación positiva 12 . La IL-6, secretada por los linfocitos T alrededor del folículo piloso, tiene un rol importante al promover la diferenciación de los linfocitos Th17 e inhibir la función de las Treg 15 . ...
... Los inhibidores de la IL-17 como el secukinumab, cumplen un rol en el inicio de la autoinmunidad, ya que esta citoquina actúa en sinergia con el TNF-α, IFN-γ e IL-1β, además de ser quien induce la producción de los autoanticuerpos, es por ello que cumple un rol fundamental en la fisiopatología de la AA 12,13 . La respuesta Th17 no solo se encuentra involucrada en una disregulación inflamatoria, también se le asocia a las comorbilidades psicológicas. ...
Article
Full-text available
Alopecia areata: a review of pathogenesis and new therapeutic targets RESUMEN La Alopecia areata (AA) es una enfermedad inflamatoria que afecta al folículo piloso produciendo pérdida de cabello no cicatrizal. Esta patología impacta negativamente la calidad de vida del paciente porque no existe tratamiento curativo ni eficaz a largo plazo, además que la respuesta a los tratamientos actuales es muy variable de persona a persona. Esto condiciona ciertos niveles de ansiedad y discapacidad en la población afectada. Es así, que en los últimos años se ha demostrado la importancia del rol inmunológico en la patogenia de la enfermedad, para poder crear nuevas dianas terapéuticas como los inhibidores de JAK, inhibidores de citoquinas, terapias que han demostrado ser seguras y eficaces. En esta revisión describimos, con un enfoque inmunológico, la patogenia de la enfermedad; así como el tratamiento convencional existente y los nuevos rumbos que está tomando el tratamiento en AA. Palabras clave: Alopecia areata, patogénesis, inmunoterapia. ABSTRACT Alopecia areata (AA) is an inflammatory disease that affects the hair follicle causing non-scarring hair loss. This pathology negatively impacts the quality of life of the patient because there is no long-term curative or effective treatment, and the response to current treatments is highly variable from person to person. This determines certain levels of anxiety and disability in the affected population. Thus, in recent years the importance of the immunological role in the pathogenesis of the disease has been demonstrated, in order to create new therapeutic targets such as JAK inhibitors, cytokine inhibitors, therapies that have demonstrated to be safe and effective. In this review we describe, with an immunological approach, the pathogenesis of the disease; as well as the existing conventional treatment and the new directions that AA treatment is taking.
... Also, the Th17 cell are accumulated around the hair follicle and in the dermis (Tojo et al, 2013), where are shown to contribute in autoimmunity of the AA (Han et al, 2015). It has detected increased IL-17A, which is implicated in several human autoimmune diseases, involving psoriasis (Ramot et al, 2018), multiple sclerosis, rheumatoid arthritis; their role in autoimmune and inflammatory diseases can clarify the higher level of serum IL-17 in AA patients (Atwa et al, 2015) the imbalance between Th17 and T regulatory cell (Treg cell) in AA may leading to inflammation and autoimmunity through resemblance pro-inflammatory mechanisms recorded in another autoimmune diseases (Noack and Miossec, 2014). ...
... AA is one of the skin disorders that are being investigated as a potential target for inhibition of IL-17, as data have accumulated on the potential role of IL-17 and Th17 in pathogenesis. Most of this data was released in the last 5 years (Ramot et al, 2018). ...
... All in all, it seems that the Th17 pathways might work in ancillary to the dominant Th1mediated responses in the induction of hair loss by providing positive feedback loops for Th1 and working as an independent source for IFNc production (Ramot et al. 2018). ...
Chapter
Alopecia areata (AA) is an autoimmune disease that targets the hair follicles (HF) and results in non-scarring hair loss. AA results from the collapse of the HF's immune privilege due to a combination of environmental and genetic factors that either change the local HF dynamics or dysregulate the central immune tolerance. Multiple genetic studies have attempted to identify AA susceptibility genes through candidate gene approaches and genome-wide analysis. These studies were able to show an association between AA and multiple immune-related genes such as those encoding cytokines, chemokines, molecules involved in regulatory T-cell functions, and adaptor molecules along with genes involved in autophagy, melanogenesis, and hair cycling pathways. This chapter aims to explore these genes and their contribution to the pathogenesis of the AA.
... 22 Loh et al. 23 reported higher serum IL-17 levels in AA patients as compared to the controls in their study. In their review, Ramot et al. 24 concluded that there is no clear relationship between IL-17 levels and disease severity or duration despite higher IL-17 levels reported in AA patients. In the present study, although IL-17 level was higher in AA patients than the controls, the difference was not statistically significant. ...
Article
Full-text available
Background: Alopecia areata (AA) is a hair disease that causes hair loss without scarring. The etiopathogenesis of AA has not been fully understood yet. Objective: To determine serum interleukin levels (IL-2, IL-4, IL-15, and IL-17) in patients diagnosed with alopecia areata and to investigate the relationship of IL levels with the duration and severity of alopecia areata and the response to tofacitinib therapy. Methods: Patients (≥16 years old) diagnosed with alopecia areata and healthy individuals as a control group was enrolled. Baseline serum interleukin levels of the patients and controls were measured. In the patient group receiving tofacitinib therapy, serum interleukin levels were measured again after 6 months. Disease severity for alopecia areata was assessed using the Severity of Alopecia Tool. Results: Sixty-one AA patients and 30 healthy individuals were included; they were comparable regarding age and sex. The mean disease duration for AA was 7 ± 6 years and the baseline mean Severity of Alopecia Tool score was 71 ± 30 (range, 20-100). Baseline IL-2, IL-4 and IL-15 levels were significantly higher in the patient group than those in the control group (p < 0.001 for each). No significant correlation was found between the baseline interleukin levels and either disease duration or disease severity (baseline Severity of Alopecia Tool score). Among the patients receiving tofacitinib (n = 22), all interleukin levels significantly decreased after treatment. However, no significant relationship between the change in interleukin levels and the change in the Severity of Alopecia Tool scores was observed after tofacitinib treatment. Study limitations: This is a monocentric study conducted in a single university hospital. Conclusion: High interleukin levels in alopecia areata patients and the significant decrease with treatment support the idea that interleukins have a role in pathogenesis. Nevertheless, no relationship could be demonstrated between IL levels and disease duration or severity.
... no clear connection between IL-17 levels and disease severity or duration. Some evidence has suggested an association between IL-17 and early-onset disease, although this awaits further confirmation [10]. ...
... IL-17 and Th17 cells are critical inducers of AA [7]. Excessive amounts of Th17 cells trigger inflammation in hair follicles, and high serum IL-17 levels are detected in patients with AA [8]. However, in certain cases, it was reported that AA develops from using IL-17 inhibitors to treat psoriasis, which can be regarded as a paradoxical reaction [9,10], and AA was ameliorated by switching to other biologics [9]. ...
Article
Full-text available
Here, we report two cases of cutaneous adverse effects possibly induced by the use of tumor necrosis factor-alpha (TNF-α) inhibitors. The first case presented alopecia areata (AA) and atopic dermatitis (AD) that developed during the treatment of ulcerative colitis using infliximab; the other case presented urticaria and AD that developed during the treatment of rheumatoid arthritis using etanercept. AA, AD, and urticaria are relatively common skin diseases; however, they are not well known as adverse effects of TNF-α inhibitors. Although immunological studies were not performed, the clinical courses suggested that these skin disorders might have developed as a result of an immune four-way imbalance in T helper 1 (Th1), Th2, Th17, and regulatory T cells by the administration of TNF-α inhibitors.
... This leads to increased production of both interleukin-17 (IL-17) and IL-22 cytokines, the main triggers of cytokine release storm (CRS) leading to the rapid and severe deterioration of the condition of patients with COVID-19 [15]. AA is itself associated with the dysregulation in systemic type 17 and type 2 cytokines, and IL-17 has been proposed as a target for AA treatment [16]. Indeed, IL-17 represents a systemic inflammatory signature of AA and, most interesting, is also reported to contribute to disease-associated psychological morbidity [17]. ...
Article
Full-text available
IntroductionThe inflammation storm involved in coronavirus disease 2019 (COVID-19) infection and worsening and the psychological stress derived from current quarantine conditions can affect the course of many skin and scalp conditions. This study examined the possible effects of COVID‐19 on alopecia areata (AA) relapse in patients suffering from these scalp conditions during the pandemic.Methods The study was carried out in the form of an observational cross-sectional type using a questionnaire sent by mail to a cohort of patients affected by AA during the pandemic from March 2020 to October 2020.ResultsDuring the pandemic, AA relapse was reported in 42.5% of the participants who also declared COVID-19 infection, confirmed by nasopharyngeal swab or hematological analysis. The relapse was reported about 2 months later COVID-19 infection (median of 2.14 months) and 74.0% of these participants continue to experience AA symptoms when the survey was proposed. Only 12.5% of participants reported AA relapse in the absence of COVID-19 infection.Conclusions The present study reported a significant relapse in patients suffering from AA and infected by COVID-19. This phenomenon could be attributed to the inflammation storm typical of COVID-19 infection and the psychological stress derived from quarantine conditions.
Article
Alopecia areata is a common condition that leads to nonscarring hair loss. It can be severe and lead to complete hair loss of the scalp or the whole body. In more severe cases, the disease can be very recalcitrant to treatment and result in a significant impairment of the quality of life of the patients. In recent years, there is increasing evidence on the potential of janus kinase (JAK) inhibitors to treat alopecia areata. In the beginning, this was based on case reports, but later, this potential was further established by large case series and in vitro and in vivo data. It is on this basis that JAK inhibitors are being tested specifically for the treatment of alopecia areata in phase 3, randomized, placebo-controlled trials, raising hopes that there will soon be a JAK inhibitor approved by the US Food and Drug Administration (FDA) for the treatment of alopecia areata. Here we provide a review of the information available on the use of JAK inhibitors to treat alopecia areata, and the potential benefits and risks of this class of medications.
Article
Background: Rosacea is a chronic inflammatory skin disease characterized with increased serum and tissue inflammatory mediators. IL-17 is a well-known inflammatory mediator that plays important roles in pathogenesis of inflammatory skin diseases. Previous studies reported that Th17 pathway is activated in rosacea and IL-17, one of Th17 signature cytokines, is elevated in tissue samples of rosacea patients. Objectives: The aim of this study was to investigate serum IL-17 levels in rosacea patients and to study its relationship with disease characteristics. Methods: Sixty patients diagnosed with rosacea and 60 healthy controls were included in the study. Serum IL-17 concentrations were measured using enzyme-linked immunosorbent assay (ELISA). Results: The mean serum IL-17 level was 8.03 pg/mL (sd=1.47) in rosacea patients and 7.37 pg/mL (sd=1.19) in controls. Serum IL-17 levels were significantly higher in rosacea (p=0.002). Serum IL-17 levels were similar among patients with erythematotelangiectatic (ET) and papulopustular (PP) rosacea (8.02 vs 8.06, p=0.83). Serum IL-17 levels did not correlate with rosacea severity (p=0.59, r=0.07 in ET rosacea; p=0.88, r=0.02 in PP rosacea), age of onset (p=0.58, r=-0.07) and disease duration (p=0.37, r=-0.11). Primary features and global assessments did not correlate with serum IL-17 levels (all p>0.05). Among secondary features, edema showed a significant negative correlation with serum IL-17 concentrations (p=0.037, r=-0.26). Conclusions: Our study showed increased serum IL-17 levels in rosacea patients and a significant correlation between IL-17 concentrations and secondary features of the disease suggesting IL-17 may contribute to pathogenesis of rosacea and may be a new target for rosacea treatment.
Article
Full-text available
It is well established that Androgenetic Alopecia (AGA) occurs in genetically predisposed individuals but little is known of its non-genetic risk factors. The aim of the study was to investigate the role of the Mediterranean diet in determining the risk of AGA. A hospital-based case-control study was conducted in the outpatient clinics of the hospital “Istituto Dermopatico dell’Immacolata, Rome, Italy”. We included 104 males and 108 controls not affected by AGA. Controls were frequency matched to cases. Information on socio-demographic characteristics, medical history, smoking and diet were collected for all patients. Logistic regression was used to estimate odds ratio and 95% confidence intervals. After controlling for age, education, body mass index and family history of AGA, protective effects for AGA were found for high consumption (≥ 3 times weekly) of raw vegetables (OR 0.43; 95% CI 0.21–0.89) and high consumption of fresh herbs (3 or more regularly) (OR 0.44; 95% CI 0.22–0.87). We suggest that some foods of the Mediterranean diet, say fresh herbs and salad, may reduce the risk of AGA onset.
Article
Full-text available
Tofacitinib is a Janus kinase 3 (JAK3) inhibitor that promotes hair growth; however, the efficacy and mechanism of this effect are not yet understood. This study aimed to evaluate the efficacy and mechanism of topical tofacitinib on hair growth in mice. Eight-week-old male C57BL/6 mice were divided equally into four groups and treated topically with tofacitinib, minoxidil, or vehicle once daily for 21 days. Weekly photographs were taken to determine the area and rate of hair growth, and tissue samples were collected for histopathological evaluation. mRNA and protein expression of anagen-maintaining growth factors, including vascular endothelial growth factor (VEGF) and insulin-like growth factor-1 (IGF-1), were determined via RT-PCR and ELISA, respectively. Tofacitinib-treated mice exhibited more hair regrowth than either minoxidil-treated or control mice did between day 7 and 21 (P < 0.05). Topical tofacitinib also promoted more rapid hair growth rate than topical minoxidil or control did (P < 0.001). Histopathology showed a distinct increase in the number of hair follicles, mostly in the anagen phase, in the tofacitinib-treated group. Hair follicles in the minoxidil- and vehicle-treated groups were more often classified as catagen and anagen. VEGF mRNA and protein expression in the tofacitinib-treated group was significantly greater than those in the other groups (P < 0.05). IGF-1 mRNA expression was not upregulated in tofacitinib-treated mice. Topical tofacitinib is effective in promoting hair growth, and the possible mechanism involves increased VEGF levels and lowered inflammation. This study will help develop a new therapeutic option for non-scarring alopecia.
Article
Full-text available
Alopecia areata is a common hair loss condition that is characterized by acute onset of non-scarring hair loss in usually sharply defined areas ranging from small patches to extensive or less frequently diffuse involvement. Depending on its acuity and extent, hair loss is an important cause of anxiety and disability. The current understanding is that the condition represents an organ-specific autoimmune disease of the hair follicle with a genetic background. Genome-wide association studies provide evidence for the involvement of both innate and acquired immunity in the pathogenesis, and mechanistic studies in mouse models of alopecia areata have specifically implicated an IFN-γ-driven immune response, including IFNγ, IFNγ-induced chemokines and cytotoxic CD8 T cells as the main drivers of disease pathogenesis. A meta-analysis of published trials on treatment of alopecia areata states that only few treatments have been well evaluated in randomized trials. Nevertheless, depending on patient age, affected surface area and disease duration, an empiric treatment algorithm can be designed with corticosteroids and topical immunotherapy remaining the mainstay of therapy. The obviously limited success of evidence-based therapies points to a more important complexity of hair loss. At the same time, the complexity of pathogenesis offers opportunities for the development of novel targeted therapies. New treatment opportunities based on the results of genome-wide association studies that implicate T cell and natural killer cell activation pathways are paving the way to new approaches in future clinical trials. Currently, there are ongoing studies with the CTLA4-Ig fusion protein abatacept, anti-IL15Rβ monoclonal antibodies and the Janus kinase inhibitors tofacitinib, ruxolitinib and baricitinib. Ultimately, the options available for adapting to the disease rather than treating it in an effort to cure may also be taken into consideration in selected cases of long-standing or recurrent small spot disease.
Article
Full-text available
Recent genetic and preclinical studies have increased our understanding of the immunopathogenesis of alopecia areata (AA). This has allowed expedited development of targeted therapies for the treatment of AA, and a paradigm shift in our approach and understanding of autoimmunity and the hair follicle. The synergy between preclinical studies, animal models, and translational studies has led to unprecedented advances in the treatment options for AA, ultimately benefiting patients who have had little recourse. In this review, we summarize the scientific field of contemporary AA research, and look forward to potential new technologies and developments.
Article
Full-text available
Hair loss known as alopecia is caused by abnormal hair follicle cycling including shortening of the anagen (growth) phase and changing of hair follicle morphology with miniaturization. In accordance with the life extension, the quality of life is considered to be a most important thing. The yearning for healthy and beautiful hair and low self esteem due to hair loss had negative influence on the quality of life with psychosocial maladjustment. The objective of this research was to identify new compound that can be used as a drug to promote hair growth. We investigated whether the function of sinapic acid (SA) is able to promote hair growth in human hair follicle dermal papilla cells (hHFDPC). We showed that treatment of SA in hHFDPC could induce proliferation and the activation of Akt signaling in HFDPC. In addition, SA could stimulate the expressions of the several growth factors, insulin-like growth factor 1, and vascular endothelial growth factor for hair growth. We showed that SA led to an increased level of phospho-GSK-3β and β-catenin accumulation in HFDPC. Finally, the promoting effect of SA in hHFDPC cell growth occurred by the induction of cell cycle progression. These results suggest that SA could be one of the potential candidate compounds for the treatment of alopecia by inducing hair growth through triggering the expressions of growth factors via activation of Akt and subsequent inactivation of GSK-3β /β-catenin pathway.
Article
Full-text available
Clinical management of alopecia represents one of the major issues in dermatology. Scalp biopsies are not easily accepted because of the high bleeding and sensitive anatomical area. Trichoscopy is routinely used for diagnosis of alopecia, but in several cases lack to provide sufficient information on the status of the disease. Recently, reflectance confocal microscopy demonstrated its usefulness for the evaluation of several inflammatory skin condition and preliminary reports about alopecia have been proposed in the literature. The aim was to identify the confocal features characterizing scarring and non-scarring alopecia. Reflectance confocal microscopy from 86 patients affected by scarring (28 lichen planopilaris and 9 lupus erythematosus) and non-scarring alopecia (30 androgenic alopecia and 19 alopecia areata), were retrospectively, blinded evaluated. Good concordance between different readers on the confocal criteria has been assessed. Statistical significant features, specific for scarring alopecia and non-scarring alopecia have been identified. In this study, data on reflectance confocal microscopy features useful for the differential diagnosis between scarring and non-scarring alopecia have been identified. Further studies focusing on the use of this non-invasive technique in the therapeutic follow-up and distinction of sub-entities of alopecia are still required.
Article
Alopecia areata (AA), a prevalent inflammatory cause of hair loss, lacks FDA-approved therapeutics for extensive cases, which are associated with very poor rates of spontaneous hair regrowth and major psychological distress. Current treatments for severe cases include broad immune-suppressants, which are associated with significant adverse effects, precluding long-term use, with rapid hair loss following treatment termination. As a result of the extent of the disease in severe cases, topical contact sensitizers and intralesional treatments are of limited use. The pathogenesis of AA is not yet fully understood, but recent investigations of the immune activation in AA skin reveal Th1/IFN-γ, as well as Th2, PDE4, IL-23, and IL-9 upregulations. Tissue analyses of both animal models and human lesions following broad-acting and cytokine-specific therapeutics (such as JAK inhibitors and ustekinumab, respectively) provide another opportunity for important insights into the pathogenesis of AA. As reviewed in this paper, numerous novel therapeutics are undergoing clinical trials for AA, emphasizing the potential transformation of the clinical practice of AA, which is currently lacking. Dermatologists are already familiar with the revolution in disease management of psoriasis, stemming from better understanding of immune dysregulations, and atopic dermatitis will soon follow a similar path. In light of these recent developments, the therapeutic arena of AA treatments is finally getting more exciting. AA will join the lengthening list of dermatologic diseases with mechanism-targeted drugs, thus changing the face of AA.
Article
Alopecia areata is an autoimmune disorder characterized by transient, non-scarring hair loss and preservation of the hair follicle. Hair loss can take many forms ranging from loss in well-defined patches to diffuse or total hair loss, which can affect all hair-bearing sites. Patchy alopecia areata affecting the scalp is the most common type. Alopecia areata affects nearly 2% of the general population at some point during their lifetime. Skin biopsies of affected skin show a lymphocytic infiltrate in and around the bulb or the lower part of the hair follicle in the anagen (hair growth) phase. A breakdown of immune privilege of the hair follicle is thought to be an important driver of alopecia areata. Genetic studies in patients and mouse models have shown that alopecia areata is a complex, polygenic disease. Several genetic susceptibility loci were identified to be associated with signalling pathways that are important to hair follicle cycling and development. Alopecia areata is usually diagnosed based on clinical manifestations, but dermoscopy and histopathology can be helpful. Alopecia areata is difficult to manage medically, but recent advances in understanding the molecular mechanisms have revealed new treatments and the possibility of remission in the near future.
Article
Background: Janus kinase (JAK) inhibitors are emerging as a promising new treatment modality for many inflammatory conditions. Objective: Our aim was to systematically review the available data on the use of JAK inhibitors in cutaneous diseases. Methods: This is a systematic review of PubMed and ClinicalTrials.gov. Results: One hundred thirty-four articles matched our search terms, of which 78 were original articles and 12 reports on adverse events. Eighteen clinical trials were found. JAK inhibitors have been extensively studied for psoriasis, showing beneficial results that were comparable to the effects achieved by etanercept. Favorable results were also observed for alopecia areata. Promising preliminary results were reported for vitiligo, dermatitis, graft versus host disease, cutaneous T cell lymphoma, and lupus erythematosus. The most common adverse events reported were infections, mostly nasopharyngitis and upper respiratory tract infections. Limitations: It was not possible to perform a meta-analysis of the results. Conclusions: This systematic review shows that while JAK inhibitors hold promise for many skin disorders, there are still gaps regarding the correct dosing and safety profile of these medications for dermatologic indications. Additional trials are necessary to address these gaps.
Article
Background: Autoimmune-triggered non-scarring hair loss is a feature of alopecia areata (AA). Initially patchy and often self-limited, severe hair loss forms include the complete loss of scalp hair or alopecia totalis (AT) and complete loss of all hair or alopecia universalis (AU). For AT and AU a reliable treatment has remained elusive. The targeted kinase inhibitor tofacitinib, in current use for treatment of other immune diseases, has been hypothesized as a viable option for AA, AT and AU therapy and a few case reports support this. Objective: Our study aims to provide evidence for the effectiveness of tofacitinib in the treatment of AU. Methods: Two patients diagnosed with long-term AU were prescribed tofacitinib citrate at a dosage of 5 mg twice daily and observed for eight months. Results: In the first patient, beard growth was significant by 3 months of treatment. By 6 months of treatment, hair growth was apparent throughout the entire body. By 8 months of treatment, scalp hair continued to grow longer and thicker. In addition, eyelashes and eyebrows were established. In the second patient, a noticeable increase in scalp hair was present just 1 month into treatment. By 4 months into treatment, significant scalp regrowth was observed as well as eyelash, eyebrow and beard regrowth. Axillary hair regrowth and isolated leg hair was noted by 8 months. Conclusion: In our patients, tofacitinib successfully alleviated AU in the absence of significant adverse side-effects. We recommend that further study be required to establish safety and confirm efficacy.