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

DOI:10.1007/s00403-018-1823-y
Authors:
Yuval Ramot at Hadassah Medical Center
Yuval Ramot
Barbara Marzani at Giuliani, Milan, Italy
Barbara Marzani
  • Giuliani, Milan, Italy
Daniela Pinto at Giuliani
Daniela Pinto
Elisabetta Sorbellini at Private Office , Milan, Italy
Elisabetta Sorbellini
  • Private Office , Milan, Italy
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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.
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Vol.:(0123456789)
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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.
... The IL-17A cytokine is associated with inflammation, which is believed to have a key role in both psoriasis and AA [4,7]. Interleukin 17 inhibitors were hoped to be a potential option for treating alopecia [7]. ...
... The IL-17A cytokine is associated with inflammation, which is believed to have a key role in both psoriasis and AA [4,7]. Interleukin 17 inhibitors were hoped to be a potential option for treating alopecia [7]. However, a recent double-blinded, randomized clinical trial showed no significant benefit for treating AA with secukinumab [8]. ...
Alopecia Areata After Initiation of Secukinumab Therapy for Plaque Psoriasis
Article
Full-text available
  • May 2023
The development of psoriasis and alopecia areata (AA) is multifactorial. The interleukin-17 (IL-17) cytokine is believed to be associated with the pathophysiology of both diseases. This case report demonstrates a 64-year-old female patient who experienced a new onset of AA after the initiation of IL-17A inhibitor, secukinumab, for the treatment of her psoriasis. To our knowledge, there are only three case reports specifically discussing IL-17A inhibitors and AA. This case report highlights a potential rare but significant side effect of IL-17A inhibitors.
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... 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]. ...
Comparison of serum concentrations of interleukins 10, 12, 17 and 35 between patients with alopecia areata and controls
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.
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... Interleukin 17 (IL 17) is an inflammatory chemokine secreted mainly by Th17 cells and other cells like neutrophils, natural killer cells and C.D 8 + T cells. Recently, the interest of finding the role of T cells in the development of autoimmune disorders increased and new targeted drugs on T cell show very promising efficacy in many auto-immune diseases like psoriatic patients (9) . Various dermoscopic features detected in AA are black dots (cadaverous hairs), yellow dots, exclamation mark hairs and broken hairs (10) . ...
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... Even if none of the clinical signs of these diseases are common with physiological aging, they share an increased aberrant IL-17-based signaling that impedes correct skin function. Alopecia areata is an autoimmune disease characterized by loss of hair in defined areas 79, 80 . This could point towards a relationship between IL-17 and HF cycling. ...
Local IL-17 orchestrates skin aging
Preprint
Full-text available
  • Jan 2022
Skin aging is characterized by structural and functional changes that lead to slower wound healing and higher rate of infections, which contribute to age-associated frailty. This likely depends on synergy between alterations in the local microenvironment and stem cell–intrinsic changes, underscored by pro-inflammatory microenvironments that drive pleotropic changes. To date, little is known about the precise nature and origin of the proposed age-associated inflammatory cues, or how they affect different tissue resident cell types. Based on deep single-cell RNA-sequencing of the entire dermal compartment, we now provide a comprehensive understanding of the age-associated changes in all skin cell types. We show a previously unreported skew towards an IL-17–expressing phenotype of Th cells, γδ T cells and innate lymphoid cells in aged skin. Aberrant IL-17 signaling is common to many autoimmune (e.g., rheumatoid arthritis and psoriasis) and chronic inflammatory diseases. Importantly, in vivo blockade of IL-17–triggered signaling during the aging process reduces the pro-inflammatory state by affecting immune and non-immune skin cells of both dermis and epidermis. Strikingly, IL-17 neutralization significantly delays the appearance of age-related traits, such as decreased epidermal thickness, increased cornified layer thickness and ameliorated hair follicle stem cell activation and hair shaft regeneration. Our results indicate that the aged skin shows chronic and persistent signs of inflammation, and that age-associated increased IL-17 signaling could be targeted as a strategy to prevent age-associated skin ailments in elderly.
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... 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). ...
The Immunogenetics of Alopecia areata
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.
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Inheritance-Specific Dysregulation of Th1- and Th17-Associated Cytokines in Alopecia Areata
Article
Full-text available
  • Aug 2023
Autoimmune diseases tend to cluster in families, suggesting genetic predisposition to autoimmunity associated with familial background. We have previously reported similarities in gene expression patterns and PTPN22 polymorphisms between alopecia areata (AA) patients and their healthy relatives, but not unrelated healthy controls. However, the spectrum of disease promoting (or preventing) pathways that may be activated in blood relatives of AA patients remains to be defined. Here, we investigated the extent to which cytokines associated with the Th1 and Th17 pathway are differentially expressed in the blood of patients with AA and its clinical subtypes in comparison to both healthy relatives as well as unrelated healthy controls. A comprehensive set of Th1- and Th17-related cytokines were evaluated by ELISA. We found a significant elevation of the Th17 inducer IL-23, the Th17 product IL-17A, the Th1 hallmark cytokine IFNγ, and TNFα, a Th1 cytokine with relevance to the Th17 pathway in AA patients, regardless of disease subtype, compared to healthy individuals. On further examination, we found that healthy family members grouped together with patients in terms of elevated Th1- and Th17-pathway cytokines in an inheritance-specific manner, distinct from unrelated controls. The elevation of Th17-associated cytokines in healthy controls related to AA patients indicates that Th1 and Th17 dysregulation in AA may be genetically based. Of note, one unrelated control displayed elevated levels of IL-17A and IL-23 similar to those detected in patients. One year after initial blood draw, areas of beard hair loss consistent with the diagnosis of AA were reported by this individual, indicating that the elevation in Th17-related cytokines may have predictive value.
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Systematic Review of Newer Agents for the Management of Alopecia Areata in Adults: Janus Kinase Inhibitors, Biologics and Phosphodiesterase‐4 Inhibitors
Article
  • Dec 2022
Management options for moderate‐to‐severe alopecia areata (AA) are limited owing to a lack of safe and effective treatments suitable for long‐term use. However, newer agents have the potential to induce and maintain hair regrowth in patients with a better side‐effects profile compared to systemic steroids or conventional systemic agents. In this article, we conducted a systematic review of newer agents, including Janus kinase (JAK) inhibitors, biologics and phosphodiesterase‐4 (PDE‐4) inhibitors, for the treatment of AA in adult patients evaluated in randomized controlled trials (RCTs) using the Severity of Alopecia Tool score. A literature search was performed on PubMed and ClinicalTrials.gov, which identified 106 items with 12 RCTs eligible for review. Information regarding the treatment regimen, duration, endpoints, efficacy and adverse events were extracted; product monograph information was also summarized for approved agents with or without indications for AA. Overall, current data suggests the oral JAK inhibitors (baricitinib, ritlecitinib, deuruxolitinib, brepocitinib) as a promising new class of agents that can induce significant hair regrowth, with mild to moderate adverse effects. Baricitinib recently received US FDA approval for the treatment of severe AA, while ritlecitinib and deuruxolitinib have received the Breakthrough Therapy designation for AA. In contrast, PDE‐4 inhibitors (apremilast) and the biologics (dupilumab, secukinumab and aldesleukin) appear to have limited efficacy thus far. Results from ongoing and future long‐term studies could shed light on the utility of the newer agents in altering the progression of AA.
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Januskinaseinhibitoren in der Therapie der Alopecia areata
Article
  • Apr 2022
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.
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Mediterranean diet: fresh herbs and fresh vegetables decrease the risk of Androgenetic Alopecia in males
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.
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Efficacy of topical tofacitinib in promoting hair growth in non-scarring alopecia: possible mechanism via VEGF induction
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.
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Alopecia Areata: a Comprehensive Review of Pathogenesis and Management
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.
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The Changing Landscape of Alopecia Areata: The Therapeutic Paradigm
Article
Full-text available
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.
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The Changing Landscape of Alopecia Areata: The Translational Landscape
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.
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Effect of sinapic acid on hair growth promoting in human hair follicle dermal papilla cells via Akt activation
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.
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Reflectance confocal microscopy for scarring and non-scarring alopecia real-time assessment
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.
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Alopecia areata
Article
  • Mar 2017
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.
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Janus kinase inhibitors in dermatology: A systematic review
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.
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Efficacy of tofacitinib in treatment of alopecia universalis in two patients
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.
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