Severe Alopecia Areata Research Articles

Treatment Patterns and Unmet Needs in the Management of Alopecia Areata: Results of a Physician's Survey in the Middle East.

Alopecia areata (AA) is an autoimmune disease characterized by nonscarring hair loss involving the scalp, face, and/or body. Literature on the prevalence, patient characteristics, management approaches, and challenges faced by patients with AA across the Middle East is limited. Therefore, a greater understanding of the current AA landscape within the region is needed. This cross-sectional study surveyed dermatologists from four countries to assess dermatologists' perspectives on the prevalence of AA within the Middle East, as well as patient characteristics, unmet needs, and management strategies. This blinded, quantitative, observational study surveyed practicing dermatologists in Egypt, Lebanon, Saudi Arabia, and the United Arab Emirates. The survey was conducted between September 2021 and January 2022 and comprised 47 closed-ended, multiple-choice questions as well as Likert scale responses. These questions assessed the characteristics of physicians and the patients in their practices, physicians' familiarity with treatment, and physicians' treatment approaches. The estimated prevalence of AA varied across the region. Across all age groups treated for AA, the majority of patients had AA of mild severity (pediatric: 63%; adolescent: 60%; adult: 54%) and the scalp was reported as the most affected area (65%). Potent topical corticosteroids were the most frequently used treatment for mild to moderate and severe AA (92% and 78%, respectively). There was a lack of awareness of investigative treatments, with only 33% of dermatologists aware of these options. The greatest unmet needs in treating AA included long-term disease control, improved efficacy, faster onset of action, and better safety profiles (62%, 53%, 52%, and 51%, respectively). This study provided insight into the diagnosis and management of AA in the Middle East. Treatment strategies were similar regardless of the severity of AA. Long-term disease control and improved efficacy and safety profiles were identified as key unmet needs in the treatment of AA.

Diagnosis and differential diagnosis of tertiary androgenetic alopecia with severe alopecia areata based on high-resolution MRI.

No previous study investigated the anatomical changes of the scalp and hair follicles between tertiary androgenetic alopecia and severe alopecia areata using high-resolution magnetic resonance imaging (HR-MRI). This study aimed to explore the value of HR-MRI in assessing alopecia. Forty-eight people were included in this study. The imaging indicators of the vertex and occipital scalp were recorded and compared. The logistic regression model was developed for the indicators that differed between tertiary androgenetic alopecia and severe alopecia areata. The receiver-operating characteristic (ROC) curve was used to assess the diagnostic efficacy of the model for tertiary androgenetic alopecia and severe alopecia areata. At the vertex, the thickness of the subcutaneous tissue layer, follicle depth, relative follicle depth, total number of follicles within a 2-cm distance, and number of strands reaching the middle and upper third of the subcutaneous fat layer within a 2-cm distance were statistically different between patients with tertiary androgenetic alopecia, those with severe alopecia areata, and healthy volunteers (p < 0.05). The logistic regression model suggested that the subcutaneous tissue layer thickness was important in discriminating tertiary androgenetic alopecia from severe alopecia areata. The ROC curve showed that the area under the curve, sensitivity, specificity, and best cutoff values of the subcutaneous tissue layer were 0.886, 94.4%, 70%, and 4.31 mm, respectively. HR-MRI can observe the changes in anatomical structures of the scalp and hair follicles in patients with alopecia. HR-MRI can be applied to the differential diagnosis of tertiary androgenetic alopecia and severe alopecia areata.

Baricitinib: A Review in Severe Alopecia Areata.

Baricitinib (Olumiant®), a Janus kinase (JAK) inhibitor, is the first drug approved for the treatment of severe alopecia areata in the USA and the EU. Severe alopecia areata is usually difficult to treat and relapse is common. Patients with this disorder are more likely to suffer from anxiety and depression. In two pivotal placebo-controlled phase 3 clinical trials in adults with severe alopecia areata, oral baricitinib once daily was associated with clinically meaningful scalp, eyebrow, and eyelash hair regrowth over 36 weeks. Baricitinib was generally well tolerated with the most common adverse events being infections, headaches, acne, and elevated levels of creatine phosphokinase. While longer-term data will be necessary to more fully understand the benefits and risks of the drug, currently available data suggest that baricitinib is a useful treatment for patients with severe alopecia areata.

Diphenylcyclopropenone and platelet-rich plasma in the management of severe or recalcitrant alopecia areata.

Alopecia areata (AA) is a common disease characterized by hair loss with an autoimmune background. There are many lines of therapy, but no standard line for all cases. Consequently, treating severe forms of AA is challenging. This study aimed to compare the efficacy and safety of the combination of diphenylcyclopropenone (DPCP) and platelet-rich plasma (PRP) with DPCP alone in treating patients with severe or refractory AA. Our randomized clinical trial was conducted on patients with severe and recalcitrant AA. Group A included 13 patients who received only DPCP, while Group B included 11 patients who received both DPCP and PRP. After sensitization in both groups of patients, DPCP was applied to half the scalp weekly. In addition, PRP injection in all scalp was performed once a month in group B. The patients in both groups completed the study for six months. The regrowth scale results were 53.85% and 54.5% for groups A and B, respectively. Although the response rate of group B was higher than that of group A, there is no statistically significant difference between the two groups. From our clinical trial, it can be concluded that DPCP alone or combined with PRP is an effective and safe method for treating severe or recalcitrant AA.

Construction of regulatory network for alopecia areata progression and identification of immune monitoring genes based on multiple machine-learning algorithms.

Alopecia areata (AA) is an autoimmune-related non-cicatricial alopecia, with complete alopecia (AT) or generalized alopecia (AU) as severe forms of AA. However, there are limitations in early identification of AA, and intervention of AA patients who may progress to severe AA will help to improve the incidence rate and prognosis of severe AA. We obtained two AA-related datasets from the gene expression omnibus database, identified the differentially expressed genes (DEGs), and identified the module genes most related to severe AA through weighted gene co-expression network analysis. Functional enrichment analysis, construction of a protein-protein interaction network and competing endogenous RNA network, and immune cell infiltration analysis were performed to clarify the underlying biological mechanisms of severe AA. Subsequently, pivotal immune monitoring genes (IMGs) were screened through multiple machine-learning algorithms, and the diagnostic effectiveness of the pivotal IMGs was validated by receiver operating characteristic. A total of 150 severe AA-related DEGs were identified; the upregulated DEGs were mainly enriched in immune response, while the downregulated DEGs were mainly enriched in pathways related to hair cycle and skin development. Four IMGs (LGR5, SHISA2, HOXC13, and S100A3) with good diagnostic efficiency were obtained. As an important gene of hair follicle stem cells stemness, we verified in vivo that LGR5 downregulation may be an important link leading to severe AA. Our findings provide a comprehensive understanding of the pathogenesis and underlying biological processes in patients with AA, and identification of four potential IMGs, which is helpful for the early diagnosis of severe AA.

Baricitinib for the Treatment of Alopecia Areata.

Alopecia areata (AA) is a relapsing, chronic, immune-mediated disease characterized by nonscarring, inflammatory hair loss that can affect any hair-bearing site. AA clinical presentation is heterogeneous. Its pathogenesis involves immune and genetic factors and several pro-inflammatory cytokines involved in AA pathogenesis, including interleukin-15 and interferon-γ, as well as Th2 cytokines, such as IL-4/IL-13, that signal through Janus kinase (JAK) pathway. AA treatment aims to stop its progression and reverse hair loss, and JAK inhibition has been shown to stop hair loss and reverse alopecia and has exhibited promising results in treating AA in clinical trials. Baricitinib, an oral, reversible, selective JAK1/JAK2 inhibitor, was shown to be superior to placebo on hair growth after 36 weeks of treatment in adults with severe AA in a phase 2 trial and recently in two phase 3 trials (BRAVE-AA1 and BRAVE-AA2). In both studies, the most common adverse events were upper respiratory tract infections, urinary tract infection, acne, headache, and elevated creatine kinase levels. On the basis of these trial results, baricitinib was recently approved by the European Medicines Agency (EMA) and USFood and Drug Administration (FDA) for the treatment of adults with severe AA. Nevertheless, longer trials are needed to determine the long-term efficacy and safety of baricitinib in AA. Current trials are ongoing and are planned to remain randomized and blinded for up to 200 weeks.

Review of efficacy of baricitinib in the treatment of alopecia areata

Alopecia areata (AA) is a long-term autoimmune condition characterized by patchy, non-scarring hair loss. It involves an autoimmune inflammatory process that gives immunity privilege to some hair follicles, while subsequent inflammatory attacks target previously normal hair follicles. One of the most important discoveries in the pathogenesis of this disease is the Janus kinase (JAK)-signal transducer and activator of the transcription (STAT) pathway. Now that a greater understanding of the immunological processes contributing to the pathogenesis has been gained, current trials’ focus was on managing the immunological reaction involved in this disease. Baricitinib is a new first-generation JAK inhibitor that has been studied in multiple trials. This study's objectives were to review existing research and summarize information on the use of Baricitinib to treat AA. The Medline database was searched for relevant published research papers using variations of the following keywords: “AA,” “Baricitinib,” and “JAK inhibitors.” The search covered studies published from 2010–2022. Our findings showed that baricitinib’s use for severe AA in multiple studies generally led to improvement of patients’ conditions with minimal side effects.

Baricitinib for alopecia areata.

Alopecia areata is a disease in which an active immune response is triggered against the hair follicles, causing hair loss. The extent of this hair loss is proportional to the number of hair follicles attacked. Alopecia areata is classified into three types depending on the area of hair fall: alopecia areata, alopecia totalis, and alopecia universalis. Alopecia areata has an approximate worldwide prevalence of 1 in 1000 people1. The current, well-known treatment of alopecia areata is intralesional corticosteroid injections, with 60-70% of patients reporting some form of hair growth afterward, while other treatments include topical immunotherapy, Minoxidil, and Anthralin2. Similar treatment methods, along with hair transplants and platelet-rich plasma (PRP) therapy, are used in Pakistan, which has been effective to some extent in controlling or stopping the progression of the condition3. Baracitinib, which has already been approved for rheumatoid arthritis and atopic dermatitis, is a Janus kinase (JAK) inhibitor that blocks the proteins known as JAK enzymes, which are involved in immune signalling and inflammation. It is unclear as to how the immune system of the body causes alopecia areata. A possible mechanism is by sending out signals that interrupt the events of hair growth. Baracitinib stops the communication among the immune cells responsible for causing hair loss which ultimately inhibits the signals mentioned above and lessens the response to injury, resulting in hair regrowth4. Thus, it can be thought of as a potential treatment for severe alopecia areata. Recently, in June 2022, FDA approved baricitinib as the first systematic treatment for alopecia areata after two clinical trials were conducted by Brett King et al. The trial showed promising results regarding the use of barticinib as after 36 weeks of exposure, oral baricitinib outperformed placebo in terms of promoting hair growth in patients with severe alopecia areata. The proportion of participants that achieved at least 80% scalp hair coverage at 36 weeks was estimated to be 38.8% with 4-mg baricitinib, 22.8% with 2-mg baricitinib, and 6.2% with placebo in trial 1 and 35.9%, 19.4%, and 3.3%, respectively, in trial 25. ---Continue

Baricitinib as the first systemic treatment for severe alopecia areata

ABSTRACT Introduction Alopecia areata is a heterogenous, immune-mediated hair loss disorder that can affect any hair-bearing site on the body. Despite being one of the most prevalent autoimmune skin diseases, treatments have historically been limited to off-label medications that have demonstrated limited efficacy, especially in more severe forms of disease. Thus, there has long been an unmet need for rigorously studied therapeutics in alopecia areata. Areas covered Janus kinase inhibitors have proven to be an effective class of drugs for treating several inflammatory disorders. One such drug, baricitinib, has recently demonstrated significant hair regrowth in phase 2 and 3 alopecia areata trials. It has since become the first systemic therapy approved for treating severe alopecia areata. This review examines the role of Janus kinase pathways in alopecia areata’s pathogenesis and the safety and efficacy of baricitinib for treating severe alopecia areata. Expert opinion The approval of baricitinib for treating severe alopecia areata marks a major milestone in the disease’s history. While baricitinib has proven to be efficacious for this indication and has demonstrated an overall good safety profile, patients’ individual risk factors for serious adverse events should be assessed during shared decision-making with patients before initiating treatment.

Trichoscopy pattern and evaluation of serum vitamin D status in alopecia areata

BackgroundVitamin D (VD) insufficiency has been linked to a number of autoimmune illnesses including, alopecia areata (AA). To distinguish between clinically common hair problems, trichoscopy is a beneficial non-invasive, rapid, and affordable procedure that is yet neglected. Objectiveto evaluate trichoscopic patterns and severity in various clinical categories of AA considering vitamin D level (VDL). Also, focusing on specific patterns of trichoscopy in AA related to VDL. Subject and methodsSeverity of Alopecia Tool (SALT) was used to clinically assess patients with AA scores. Trichoscopic patterns were analyzed concerning VDL and disease severity. The VDL was estimated for 59 patients and 60 healthy controls. ResultsVDL was higher in healthy controls than in AA patients. The most common trichoscopic findings seen in our study were yellow dots (77.97%), followed by black dots (67.8%), and broken hairs (59.32%). Short vellus hairs and yellow dots were the most common in remitting AA. In progressive AA, the most common findings were broken hairs, yellow dots, and tapering hairs. VDL was significantly higher in both mild and moderate AA. ConclusionsVDL was significantly lower in severe AA and active progressive disease. Trichoscopic features could predict disease activity and VDL in patients with AA. Broken and tapering hairs will be more represented in patients with progressive disease. Short vellus hairs were seen more in stable or remitting disease. Furthermore, black dots and broken hairs were more prevalent in AA with deficient VDL.

Scalp Hair Regrowth Is Associated With Improvements in Health-Related Quality of Life and Psychological Symptoms in Patients With Severe Alopecia Areata: Results From Two Randomized Controlled Trials

Scalp Hair Regrowth Is Associated With Improvements in Health-Related Quality of Life and Psychological Symptoms in Patients With Severe Alopecia Areata: Results From Two Randomized Controlled Trials

Trajectories For Scalp Hair Regrowth In Patients With Severe Alopecia Areata Treated With Baricitinib

Trajectories For Scalp Hair Regrowth In Patients With Severe Alopecia Areata Treated With Baricitinib

Baricitinib-related AEs in patients with severe alopecia areata

Baricitinib-related AEs in patients with severe alopecia areata

Safety of baricitinib in adults with severe alopecia areata.

Safety of baricitinib in adults with severe alopecia areata.

MicroRNA-1246 Inhibits NFATc1 Phosphorylation and Regulates T Helper 17 Cell Activation in the Pathogenesis of Severe Alopecia Areata.

We found microRNA (miR)-1246 to be significantly differentially expressed between severe active alopecia areata (AA) patients and healthy individuals. To explore the role and mechanism of miR-1246 in severe AA. Expression of miR-1246, dual-specific tyrosine phosphorylation-regulated kinase 1A (DYRK1A), and nuclear factor of activated T cells 1c (NFATc1) in peripheral CD4+ T cells and in scalp tissues of patients were detected using RT-qPCR, Western blot, and immunohistochemistry assays. Peripheral CD4+ T cells from the AA patients were transfected with lentiviral vectors overexpressing miR-1246. RT-qPCR and Western blot analysis were used to measure mRNA or protein expression of retinoic-acid-receptor-related orphan nuclear receptor gamma (ROR-γt), interleukin (IL)-17, DYRK1A, NFATc1, and phosphorylated NFATc1. Flow cytometry was used to assay the CD4+IL-17+ cells proportion. ELISA was used to measure cytokine levels. miR-1246 levels decreased and DYRK1A and NFATc1 mRNA levels significantly increased in the peripheral CD4+ T cells and scalp tissues of severe active AA samples. NFATc1 protein expression was also significantly increased in the peripheral CD4+ T cells but not in the scalp tissues. NFATc1 positive cells were mainly distributed among infiltrating inflammatory cells around hair follicles. In peripheral CD4+ T cells of severe active AA, overexpression of miR-1246 resulted in significant downregulation of DYRK1A, NFATc1, ROR-γt, and IL-17 mRNA and phosphorylated NFATc1 protein, as well as a decrease in the CD4+IL-17+ cells proportion and the IL-17F level. miR-1246 can inhibit NFAT signaling and Th17 cell activation, which may be beneficial in the severe AA treatment.

Guidelines for the Management of Patients with Alopecia Areata in Korea: Part II Systemic Treatment.

Alopecia areata (AA) is a chronic disease with an unpredictable course and can have a severe psychological impact on an individual. To provide evidence and consensus-based statements regarding the treatment of patients with AA in Korea. We searched for relevant studies from inception to May 2021 regarding the systemic treatment of AA. Evidence-based recommendations were also prepared. The evidence for each statement was graded and classified according to the strength of the recommendations. Hair experts from the Korean Hair Research Society (KHRS) voted on the statement, and an agreement of 75% or greater was considered as having reached consensus. Current evidence supports the efficacy of systemic corticosteroids, oral cyclosporine monotherapy or combination with systemic corticosteroids, and oral Janus kinase inhibitors in severe AA patients. Systemic steroids may be considered for pediatric patients with severe AA. A consensus was achieved in three out of nine (33.3%), and one out of three (33.3%) statements pertaining to systemic treatment in adult and pediatric AA, respectively. The present study produced up-to-date, evidence-based treatment guidelines for AA associated with the consensus obtained by experts based on the Korean healthcare system.

Which is the Ideal JAK Inhibitor for Alopecia Areata - Baricitinib, Tofacitinib, Ritlecitinib or Ifidancitinib - Revisiting the Immunomechanisms of the JAK Pathway.

Alopecia areata (AA) is an immune-mediated condition, clinically manifesting as non-cicatricial patches of alopecia. It is often a self-limiting condition; however, regrowth of hair can take a long period of time, resulting in significant psychological comorbidity. With the recent advances in pathomechanisms of AA, the therapeutic approach to the condition has become more specific, and targeted therapy with small molecules is probably the ideal intervention. Many therapies exist for AA, but none of the systemic agents were approved, until recently, when baricitinib (Janus kinase (JAK1 and JAK2 inhibitor) gained FDA approval for the treatment of adult patients with severe AA. JAK inhibitors (JAKibs) target the γc cytokine and interferon-gamma (IFN-γ) signaling pathway, which is critical to the immunopathogenesis of AA and thus can reverse the hair loss in AA. Although JAKibs are emerging as a promising treatment modality for AA, the ideal JAKib is not yet settled, as there is scant data on H-2-H (head-to-head) comparisons of JAK inhibitors in AA. Moreover, the response achieved with JAKibs is not sustained after treatment discontinuation, with many studies showing a high recurrence rate with tofacitinib and ruxolitinib post-treatment. Also, recent studies have hypothesized that JAK2, with its ubiquitous expression, can cause adverse effects, unlike JAK1, which is associated with multiple major cytokine receptor families and JAK3, which is exclusively associated with the γc cytokine receptor. Thus, JAK3ibs may be associated with a better side effect profile and, in conjunction with their specificity, may replace other JAKibs as the treatment of choice for AA. We herein discuss the role of the JAK/STAT (signal transducer and activator of transcription) pathway in AA, the intricacies of various JAKibs in the management of AA, and emphasize the need for studies on tissue JAK and cytokine expression before arriving at the ideal JAKibs for AA.

Evaluation of Sleep Disturbance in Alopecia Areata through Questionnaire: Pittsburgh Sleep Quality Index as a Reasonable Tool.

Alopecia areata (AA) is common non-scarring hair loss disease. Sleep distrubance has been regarded as a triggering or aggravating factor for AA. However, objective evaluation of sleep disturbance and its clinical effect on AA has not been clearly demonstrated. This study investigated objective sleep evaluation tool for AA patients and their clinical correlation. Patients presenting with new-onset AA or recurrences of pre-existing AA were included, and those who reported sleep disturbance in the preliminary survey were designated as the sleep disturbance group (SD group). Sleep quality was investigated for them using three self-administered questionnaires: Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI), and Epworth Sleep Scale (ESS). Demographic information and clinical features of AA were analyzed according to sleep quality. A total of 400 participants were enrolled, and 53 were categorized into the SD group. The incidence of stressful events was significantly higher in the SD group (54.7%) than in the non-SD group (25.1%) (p<0.001). Based on the PSQI, 77.3% of participants were objective poor sleepers (score of 5 or more), and they showed a significantly higher incidence of stressful events compared to good sleepers (p=0.019). The proportion of poor sleepers was significantly lower in patients with mild AA (S1) than in those with moderate to severe AA (S2~S5) (p=0.045). This study demonstrated a positive correlation among stress, SD, and AA. The degree of SD was objectively represented by the PSQI score, showing different scores according to AA severity.

Integrated safety analysis of baricitinib in adults with severe alopecia areata from two randomized clinical trials.

Baricitinib, an oral, selective, reversible Janus kinase (JAK)1/JAK2 inhibitor, is an approved treatment for adults with severe alopecia areata (AA) in the USA, European Union and Japan. To report safety data for baricitinib in patients with severe AA from two clinical trials including long-term extension periods. This analysis includes pooled patient-level safety data from two trials, an adaptive phase II/III trial (BRAVE-AA1) and a phase III trial (BRAVE-AA2) (ClinicalTrials.gov, NCT03570749 and NCT03899259). Data are reported in three datasets: (i) the placebo-controlled dataset (up to week 36): baricitinib 2 mg and 4 mg vs. placebo; (ii) the extended dataset (up to the data cutoff): patients remaining on continuous treatment with baricitinib 2 mg or 4 mg from baseline; and (iii) the all-baricitinib dataset (all-BARI, up to the data cutoff): all patients receiving any dose of baricitinib at any time during the trials. Safety outcomes include treatment-emergent adverse events (TEAEs), adverse events of special interest and abnormal laboratory changes. Proportions of patients with events and incidence rates (IR) were calculated. Data were collected for 1303 patients who were given baricitinib, reflecting 1868 patient-years of exposure (median 532 days). The most frequently reported TEAEs during the placebo-controlled period (based on the baricitinib 4-mg group) were upper respiratory tract infection, nasopharyngitis, headache, acne and elevated blood creatine phosphokinase (CPK). During the placebo-controlled period, the frequency of acne was higher with baricitinib than placebo, and elevated CPK was higher with baricitinib 4 mg than placebo and baricitinib 2 mg. In all-BARI, the IR of serious infections was low (n = 16, IR 0.8). There was one opportunistic infection (IR 0.1), and 34 cases of herpes zoster (IR 1.8). There was one positively adjudicated major adverse cardiovascular event (myocardial infarction) (IR 0.1), one pulmonary embolism (IR 0.1), three malignancies other than nonmelanoma skin cancer (IR 0.2) and one gastrointestinal perforation (IR 0.1). No deaths were reported. This integrated safety analysis in patients with severe AA is consistent with the overall safety profile of baricitinib. Some differences with atopic dermatitis were noted that may be attributable to the disease characteristics of AA.

Prevalence, comorbidities, and treatment patterns of Japanese patients with alopecia areata: A descriptive study using Japan medical data center claims database.

Real-world data on alopecia areata (AA) demographics, comorbidities, and treatment patterns are sparse, not only in Japan but worldwide. This cross-sectional study assessed the current prevalence of AA in Japan, including analysis of severe subsets, frequency of comorbidities, and unmet medical needs surrounding treatment. Patients registered in the Japan Medical Data Center claims database (January 2012 to December 2019) and diagnosed with AA were included. Prevalence was calculated yearly, with the most common comorbidities evaluated, and treatments described in the Japanese Dermatological Association AA management guidelines and approved in Japan were included in the analysis. In total, 61 899 patients were diagnosed with AA. Among them, 1497 were diagnosed with severe subtypes. AA prevalence in Japan has been gradually increasing (from 0.16% in 2012 to 0.27% in 2019). The most common comorbidities are allergic rhinitis, atopic dermatitis, and asthma. Depression and anxiety are frequent in these patients, as are autoimmune diseases, e.g., vitiligo, thyroid diseases, and rheumatoid arthritis. Intriguingly, the analysis found Down syndrome to be a comorbidity associated with severe AA in children. The principal treatments were topical corticosteroids, followed by carpronium chloride and cepharanthine. The use of systemic corticosteroids and antihistamines is increased in severe disease. The Japanese Dermatological Association guidelines do not support the use of oral corticosteroids in children; however, in the database, this has been prescribed in up to 2.5% and 9.8% of all pediatric and severe pediatric AA cases, respectively. Despite the limitations of using a claims database, the current study demonstrates that AA prevalence in Japan has gradually increased in recent years, with allergic diseases being the most common comorbidities. The data also imply that there is a need for effective and safe therapies, especially for severe and pediatric cases.