Cases analysis and etiology discussion of thymoma with alopecia areata / 中华胸心血管外科杂志

Objective:Analyzed the clinicopathological features of thymoma with alopecia areata, and discussed the pathogenesis and treatment methods.Methods:The clinicopathologic data of patients with thymoma who underwent surgery from August 1, 2015 to July 31, 2020 in Beijing Tongren Hospital, Capital Medical University were reviewed. Transversally analyzed the patients of thymoma with alopecia areata and longitudinally compared with the patients of thymoma without alopecia areata after 1﹕10 matched by propensity score matching.Results:A total of 252 patients of thymoma were enrolled, including 6 patients with alopecia areata, accounting for 2.38%. The anti-AchR antibody, CD4 + /CD8 + T inversion in serum and myasthenia gravis were present in the all 6 thymoma patients with alopecia areata, which were significantly higher than those in the group of thymoma without alopecia areata. Besides myasthenia gravis, the proportion of complicated with other autoimmune diseases in thymoma patients with alopecia areata was significantly higher than that of thymoma patients without alopecia areata[83.33%(5/6) vs. 20.00%(12/60), P=0.003]. After operation, 5 patients’ alopecia areata were improved in 6 thymoma patients with alopecia areata(83.33%, 5/6). Conclusion:The thymoma patients with alopecia areata always complicated with myasthenia gravis and other autoimmune diseases. The pathogenesis may be associated with autoimmune CD8 + T lymphocytes produced by thymoma. At present, surgery is still the most effective way to improve thymoma-associated alopecia areata.

Study on the Traditional Chinese Medicine Syndromes of 800 Children with Alopecia Areata Based on Factor Analysis and Cluster Analysis / 中医杂志

ObjectiveTo study the traditional Chinese medicine （TCM） syndromes of children with alopecia areata， and provide evidence for TCM differentiation and treatment in clinic. MethodsA retrospective analysis was conducted on the clinical data of 800 children with alopecia areata admitted to the Hair Medicine Center of the China-Japan Friendship Hospital from January 1， 2012 to December 31， 2021. The clinical data of the children were collected using a four-examination information questionnaire， including clinical characteristics （age of consultation， age of onset， course of disease， family history， severity grading）， alopecia areata-related factors （triggers）， and four-examination information （including sleep， diet， emotions， bladder and bowel function， etc.）. Descriptive frequency analyses， rank sum tests， factor analyses and cluster analyses were performed， and the distribution of the major TCM syndromes was summarised with the clinical data. ResultsThere were 800 children with alopecia areata， including 449 males and 351 females； 8 cases （1.00%） were in infancy， 36 cases （4.50%） were in early childhood， 180 cases （22.50%） were in preschool， 380 cases （47.50%） were in school age， and 196 cases （24.50%） were in puberty at the time of consultation； the average age of consultation was 8.31±3.86 years， the average age of onset of disease was 5.40±3.82 years， and the average duration of disease was 2.94±2.77 years； 527 children （65.87%） with severe alopecia areata； 85 children （13.56%） had a family history of alopecia areata； 772 children （96.50%） had unknown triggers for their first alopecia areata， and 28 children （3.50%） reported the presence of obvious triggers， including fright （9 cases）， high fever （5 cases）， allergic reactions （4 cases）， micronutrient （zinc， iron， etc.） deficiencies （4 cases）， inappropriate diet （2 cases）， environmental factors （1 case， new house renovation）， atopic dermatitis （1 case）， atopic asthma （1 case）， and pneumonia （1 case）. A total of 40 four-examination information items were collected， among which the frequency of kicking quilts was the highest with 380 cases （47.50%）， followed by picky eating （369 cases， 46.13%）， sleeplessness （334 cases， 41.75%）， irritability （334 cases， 41.75%）， partiality towards certain foods （306 cases， 38.25%）， impulsiveness （297 cases， 37.13%）， dry stools （233 cases， 29.13%）， yellow urine （215 cases， 26.88%）， nail biting （213 cases， 26.63%）， bad breath （211 cases， 26.38%）. According to factor analysis and cluster analysis， five types of TCM syndromes were obtained， in order as qi and blood deficiency syndrome （110 cases， 13.75%）， spleen deficiency syndrome （114 cases， 14.25%）， kidney essence deficiency syndrome （140 cases， 17.50%）， dietary stagnation syndrome （150 cases， 18.75%）， and liver depression and spleen deficiency syndrome （286 cases， 35.75%）. Patients in each age group and SALT grading are mainly liver depression and spleen deficiency syndrome. ConclusionThe TCM symptoms of children with alopecia areata are mainly based on qi and blood deficiency syndrome， spleen deficiency syndrome， kidney essence deficiency syndrome， dietary stagnation syndrome， and liver depression and spleen deficiency syndrome， of which liver depression and spleen deficiency syndrome is the most common type at different ages and stages of the disease.

Adiponectin serum levels and ADIPOQ (rs2241766) polymorphism in alopecia areata Egyptian patients

Abstract Background Alopecia Areata (AA) is an acquired autoimmune form of non-scarring hair loss. Adiponectin and its gene polymorphism were related to many autoimmune disorders. Objective Assessment of adiponectin serum levels and adiponectin gene (ADIPOQ) (rs2241766) Single Nucleoid Polymorphism (SNP) in AA patients and correlating the results with the disease severity in those patients. Methods This study included 75 AA patients and 75 age and gender-matched healthy subjects (controls). The severity of Alopecia Tool (SALT) score assessment to evaluate AA severity was done. Adiponectin serum levels by ELISA and ADIPOQ (rs2241766) SNP using PCR were performed. Results Adiponectin serum levels were significantly lower in AA patients than controls (p = 0.001). ADIPOQ (rs2241766) TG genotype and G allele were significantly predominant in AA patients increasing its risk by 5 and 4 folds (OR = 5.17, p = 0.001), (OR = 3.82, p = 0.001) respectively. Serum adiponectin levels were negatively correlated with SALT score (r = -0.435, p = 0.001) and associated with alopecia totalis (p = 0.016). ADIPOQ (rs2241766) TG genotype was significantly associated with low serum adiponectin levels and higher SALT score (p = 0.001). Study limitations The small sample size. Conclusions ADIPOQ (rs2241766) gene polymorphism (TG genotype and G allele) may modulate AA risk and contribute to the development of AA in Egyptian populations. Decreased circulating adiponectin levels may have a dynamic role in AA etiopathogenesis. Adiponectin serum concentration can be considered a severity marker of hair loss in AA.

Oxidative stress and antioxidant markers in patients with alopecia areata: A comparative cross-sectional study

Background: Alopecia areata is a chronic inflammatory skin disease. Oxidative stress may contribute to the pathogenesis of this condition. Aim: To evaluate the serum oxidative stress markers and antioxidant capacity in patients with alopecia areata. Methods: This cross-sectional study was performed on 40 patients with alopecia areata and 40 healthy controls. The fasting blood sugar, C-reactive protein, lipid profile, and serum oxidative markers, including advanced glycation end products and advanced oxidation protein products, were measured in this study. Also, antioxidant enzymes, including paraoxonase-1, lecithin-cholesterol acyltransferase and serum ferric-reducing antioxidant power, were determined. Results: The serum levels of advanced glycation end products and advanced oxidation protein products were significantly higher in patients with alopecia areata, compared to the controls (P < 0.001), whereas the levels of ferric-reducing antioxidant power, paraoxonase-1 and lecithin-cholesterol acyltransferase were significantly lower in patients with alopecia areata, compared to the controls (P < 0.001). The mean fasting blood sugar level was significantly higher in patients with alopecia areata, compared to the controls. The ferric reducing antioxidant power level was significantly associated with the percentage of hair loss (P = 0.01, r = 0.4) and the serum C-reactive protein level (P = 0.03, r = –0.3) in patients with alopecia areata. Limitations: Since the current study had a cross-sectional design, no cause-effect relationship was established between alopecia areata and oxidative stress. The sample size of our study was also small. Conclusion: Based on the present results, the oxidant-antioxidant enzymatic system is impaired in alopecia areata due to the increased oxidative products and decreased antioxidant activity

Inhibidor janus kinasa como opción terapéutica en alopecia areata. Reporte de caso / Janus kinase inhibitor as a therapeutic option in alopecia areata. Case report

RESUMEN La alopecia areata (AA) es una enfermedad autoinmune que genera pérdida no cicatrizal de cabello con diferentes grados de afectación, incluyendo la pérdida total de los tallos pilosos. A pesar de ser una entidad benigna, tiene un gran impacto en el ámbito emocional y psicosocial de los pacientes. En la actualidad, se dispone de una amplia variedad de tratamientos tanto tópicos como orales. Se presenta el caso de una paciente de 24 años, con alopecia areata recurrente severa, sin respuesta a múltiples tratamientos previamente prescritos, en quien se descartó una causa secundaria y se confirmó diagnóstico histológico con biopsia. Se inició tratamiento con tofacitinib, un inhibidor de la JAK, con una excelente respuesta clínica al mes de iniciado el tratamiento.

A B S T R A C T Alopecia areata (AA) is an autoimmune disease that generates non-scar loss of hair with varying degrees of involvement, including total loss of hair follicles. Despite being a benign entity, it has a great impact on the emotional and psychosocial life of patients. A wide variety of topical and oral treatments are currently available. We present the case of a 24-year-old patient with severe recurrent alopecia areata without response to multiple pre vious treatments, in which a secondary cause was ruled out and the histological diagnosis was confirmed with biopsy. Treatment with tofacitinib, a JAK inhibitor, was started, showing an excellent clinical response after one month of treatment.

Distribution of Traditional Chinese Medicine Syndromes in 600 Patients with Alopecia Areata Based on Factor Analysis and Cluster Analysis / 中医杂志

ObjectiveTo explore the distribution of traditional Chinese medicine （TCM） syndromes of alopecia areata （AA）， and to provide reference for TCM clinical syndrome differentiation and classification of AA. MethodsAA patients who visited the specialized hairiness clinic of Beijing China-Japan Friendship Hospital were included. A questionnaire was developed including general information of the patients， history of hair loss （onset time， triggers and exacerbating factors， disease progression）， current symptoms （symptoms and signs）， medical history， personal history， family history， and hair microscopy examination results. The factor analysis and cluster analysis were used to determine the syndrome elements and to summarize the syndrome types. ResultsA total of 600 patients with AA were included， including 218 males （36.33%） and 382 females （63.67%）. Totally， 128 patients （21.33%） had a family history of hair loss， and 326 patients （54.33%） had a previous related underlying disease. The leading triggering and exacerbating factors of AA were tension and anxiety， accounting for 335 cases （55.83%） and 285 cases （47.50%）， respectively. The top 10 symptoms involved among patients were scalp oil， anxiety， irritability， dreaminess， fatigue， itching， tension， weakness and dandruff. The factor analysis showed that the factor rotation converged after 9 iterations， and finally obtained 12 common factors and 34 variables， with a cumulative contribution rate of 58.59%. In terms of disease location of AA， the main syndrome elements were liver， spleen and kidney， and the disease nature syndrome elements were mainly dampness-heat， qi stagnation， yin deficiency， qi deficiency， and blood deficiency. The clustering analysis of the 12 common factors showed that TCM syndromes could be summarized into four categories： internal retention of damp-heat， liver-kidney deficiency， qi and blood deficiency， and liver constraint and spleen deficiency. There were significant differences in the distribution of TCM syndromes in patients of different ages and genders （P＜0.001）. ConclusionThe main disease location of AA is in the liver， spleen， and kidney， with the liver being the key. The disease mechanism of AA is a deficiency-excess complex， initially manifested as excess and later becoming deficiency. The TCM syndromes mainly include four types which are internal retention of damp-heat， liver-kidney deficiency， qi and blood deficiency， and liver constraint and spleen deficiency.

Analysis of the Anastomosis between the Animal Model of Alopecia Areata and the Characteristics of Clinical Disease / 世界科学技术-中医药现代化

In this study,the existing animal models of alopecia areata were systematically summarized based on literature review and disease and syndrome characteristics assignment method,and the clinical anastomosis was analyzed.The results showed that cell induction and skin transplantation had a high anastomosis with the clinic,and the anastomosis was as high as 80%.The anastomosis between imiquimod cream and cyclophosphamide induced alopecia areata was 72%.C3H/HeJ mice and C57BL/6 mice were selected as the first choice in terms of the pathogenesis of alopecia areata disease,pathogenic factors,replicability,convenience and practicability of the model.Other SCID mice,B6.KM-AA mice,SD rats and BALB/c mice can be selected appropriately according to the content and period of the experimental study of alopecia areata.It is found that the existing models of alopecia areata mainly rely on Western medicine,lack of pathogenic factors of traditional Chinese medicine,and the model of combining disease and syndrome of alopecia areata is not widely used in practice.Based on this,it is suggested that the animal model of"combination of disease and syndrome"should be considered in the subsequent construction of alopecia areata model to make it more suitable for clinical characteristics of disease and syndrome.We can add the relevant indicators of different syndrome types of liver and kidney insufficiency,blood stasis and maoqiao,blood deficiency and blood heat and other pathogenic factors,and add the apparent indicators of animal mental state,diet and water intake,behavior,etc.,to improve the animal model of alopecia areata which is highly consistent with the clinical characteristics of traditional Chinese and western medicine.

Comparison of the latest Chinese and international guidelines/consensus on diagnosis and treatment of alopecia areata / 中华皮肤科杂志

Nowadays, various countries have developed guidelines/consensus on the diagnosis and treatment of alopecia areata. Differences between these guidelines/consensus may reflect differences in backgrounds, research status, medical resources and clinical traditions among countries. This review compares Chinese and international guidelines/consensus on the diagnosis and treatment of alopecia areata in the past 3 years, and analyzes the epidemiology, etiology, diagnosis, severity assessment methods and treatment of alopecia areata, so as to provide a reference for standardized and individualized diagnosis and treatment of alopecia areata in China.

Janus kinase inhibitors for the treatment of five children with severe alopecia areata / 中华皮肤科杂志

Objective:To evaluate the efficacy of Janus kinase (JAK) inhibitors in the treatment of 5 children with severe alopecia areata, especially those with complicated nail damage.Methods:A total of 5 children with severe alopecia areata were enrolled and treated with oral JAK inhibitors (tofacitinib or baricitinib). The improvement of hair loss was assessed by using the severity of alopecia tool (SALT) at 12, 24, 36, and 48 weeks after the start of treatment. For 3 children with complicated nail damage, the improvement of diseased nails and toenails was evaluated by using the modified nail psoriasis severity index after treatment. During the treatment, adverse reactions were monitored.Results:The 5 children with severe alopecia areata were aged 2 - 11 years, with the disease duration ranging from 5 to 120 months, and the treatment with JAK inhibitors lasted 24 - 48 weeks. After 12-week treatment, 2 children achieved a 50% improvement in SALT (SALT50) ; after 24-week treatment, 3 achieved SALT95, and 1 achieved SALT75 and then withdrew baricitinib for personal reasons; after 36-week treatment, 3 achieved SALT99, and then received half-dose treatment; after 48-week treatment, 1, 1, 1 and 1 patient achieved SALT99, SALT83, SALT31, and SALT0, respectively, and 2 of them experienced gradually aggravated hair loss 1 - 2 months after the start of half-dose treatment. Among the 3 children with complicated nail damage, the improvement rates of nail severity index scores were 67.5%, 45.4%, and 25% respectively, and the improvement rates of toenail severity index scores were 42.5%, 71.4%, and 5% respectively after 12-week treatment; after 48-week treatment, the improvement rate of nail severity index scores were 100%, 100%, and 50% respectively, and the improvement rate of toenail severity index scores were 96.2%, 100%, 50% respectively. During the treatment, the uric acid level increased in 2 children, and one of them was accompanied by increased serum levels of low-density lipoprotein cholesterol and high-density lipoprotein cholesterol; 1 suffered from respiratory tract infections twice during the treatment, and was recovered after symptomatic treatment; there were no adverse reactions leading to drug withdrawal.Conclusion:JAK inhibitors can be used as a treatment option for severe alopecia areata in children.

JAK-STAT pathway inhibitors in dermatology

Abstract The JAK-STAT signaling pathway mediates important cellular processes such as immune response, carcinogenesis, cell differentiation, division and death. Therefore, drugs that interfere with different JAK-STAT signaling patterns have potential indications for various medical conditions. The main dermatological targets of JAK-STAT pathway inhibitors are inflammatory or autoimmune diseases such as psoriasis, vitiligo, atopic dermatitis and alopecia areata; however, several dermatoses are under investigation to expand this list of indications. As JAK-STAT pathway inhibitors should gradually occupy a relevant space in dermatological prescriptions, this review presents the main available drugs, their immunological effects, and their pharmacological characteristics, related to clinical efficacy and safety, aiming to validate the best dermatological practice.

Comorbilidades y factores asociados en pacientes con alopecia areata / Comorbidities and associated factors in patients with alopecia areata i: en

Introducción: La alopecia areata en una enfermedad autoinmune caracterizada por la pérdida no cicatricial de pelo; puede ser catalogada como un problema estético, sin tener en cuenta que tiene alto impacto en la calidad de vida de quien la padece. Objetivo: Identificar las comorbilidades, el impacto psicosocial y los factores asociados en pacientes con alopecia areata. Métodos: Se realizó un estudio observacional, descriptivo y transversal de 50 pacientes con diagnóstico clínico de alopecia areata, atendidos en el Hospital General Docente Dr. Juan Bruno Zayas Alfonso de Santiago de Cuba, desde 2018 hasta 2020. Resultados: En la casuística prevalecieron los pacientes de 29-39 años de edad (46,0 %), el sexo masculino (58,0 %), el estrés y la ansiedad como factores emocionales (76,0 %), seguidos de los focos sépticos (40,0 %); el nivel de escolaridad de técnico medio (52,0 %), el estado civil acompañado (44,0 %) y el tiempo de evolución de la alopecia entre 4 y 12 meses (76,0 %). Conclusiones: Se evidenció que la mayoría de los pacientes presentaron algún episodio emocional o una crisis de ansiedad, previos al inicio de la alopecia areata.

Introduction: The alopecia areata in an autoimmune disease characterized by the non-cicatricial loss of hair; that can be classified as a cosmetic problem, without taking into account that has high impact in the life quality of the one who suffers from the disease. Objective: To identify the comorbidities, psychosocial impact and associated factors in patients with alopecia areata. Methods: An observational, descriptive and cross-sectional study of 50 patients with clinical diagnosis of alopecia areata was carried out, they were assisted in Dr. Juan Bruno Zayas Alfonso Teaching General Hospital in Santiago de Cuba, from 2018 to 2020. Results: In the case material there was a prevalence of the 29-39 years patients (46.0 %), the male sex (58.0 %), stress and anxiety as emotional factors (76.0 %), followed by the septic focus (40.0 %); the school level of technician (52.0 %), accompanied as marital status (44.0 %) and the time of evolution of the alopecia between 4 and 12 months (76.0 %). Conclusions: It was evidenced that most of the patients presented some emotional event or a crisis of anxiety before the beginning of the alopecia areata.

EVALUATION OF THYROID PROFILE IN THE INDIAN POPULATION WITH ALOPECIA AREATA

Alopecia areata is an autoimmune disease that causes hair loss. It is characterized by patchy hair loss that affects the scalp and other areas of the head, as well as the eyelashes, beard, and complete body hair. Alopecia areata manifests as a circular patch of hair loss that may progress to baldness of the entire scalp (Alopecia areata totalis) or loss of full body hair (Alopecia areata universals). The disease's etiopathogenesis is unknown, however autoimmunity appears to play a signi?cant role. Thyroid problems are frequently linked to AA, the most common of which is autoimmune Thyroid disorders. Aim: The goal of our research is to see if Alopecia Areata (AA) is linked to thyroid hormones (T3, T4, and TSH) and to evaluate the T3, T4, and TSH levels. Material and Methods: The present study included 150 A.A patients(cases) and 150 controls attended to Department of Dermatology in collaboration with Department of Biochemistry, LNMC & J.K Hospital, Bhopal. The levels of T3, T4 and TSH was estimated by ELISA. Result: The present study shows statistically signi?cant differences between patients and controls regarding Thyroid Hormones levels of TSH, T3 and T4. Conclusions: The ?ndings imply an association between Alopecia Areata and Thyroid function issues. Thyroid function abnormalities should be checked in all patients with alopecia areata, regardless of their clinical condition

Stem cell therapy for alopecia areata / 中华皮肤科杂志

It is currently considered that alopecia areata is caused by the impairment of immune privilege in hair follicles. Stem cells have immunoregulatory functions, and can secrete a variety of cytokines to promote immune privilege in hair follicles. Stem cell therapy, especially umbilical cord- and adipose-derived stem cell therapy, has been applied to a variety of preclinical and clinical studies on alopecia, providing a new approach to refractory alopecia areata.

Regulatory effect of interleukin-18 on natural killer cell activity in patients with alopecia areata / 中华皮肤科杂志

Objective:To investigate changes of natural killer (NK) cell subsets and interleukin-18 (IL-18) level in peripheral blood of patients with alopecia areata, and to assess the regulatory effect of IL-18 on NK cell activity.Methods:A total of 67 patients with alopecia areata (alopecia areata group) and 25 healthy volunteers (control group) were collected from Shanxi Provincial People′s Hospital between December 2019 and January 2021. Peripheral blood mononuclear cells (PBMCs) and plasma were isolated. The percentage of NK cell subsets was investigated by flow cytometry, and plasma IL-18 level was measured by enzyme-linked immunosorbent assay. PBMCs were stimulated with recombinant human IL-18, and co-culture systems of PBMCs with 721.221 cells, K562 cells and P815-Ab cells were established separately. NK cell function was assessed by determining the percentage of CD107a-expressing NK cells and fluorescence intensity of CD16 + NK cells. Comparisons between groups were performed using t test or paired t test. Results:Compared with the control group, the alopecia areata group showed significantly decreased percentage of CD56 +CD16 - NK cells (8.12% ± 3.14% vs. 10.78% ± 4.08%, t = 3.33, P = 0.001) , but significantly increased percentage of CD56 +CD16 + NK cells (46.08% ± 15.21% vs. 32.14% ± 10.45%, t = 4.22, P < 0.001) , and there was no significant difference in the percentage of CD56 -CD16 + NK cells between the alopecia areata group and control group (28.81% ± 8.65% vs. 27.09% ± 7.62%, t = 0.88, P = 0.383) . The plasma IL-18 level was significantly higher in the alopecia areata group than in the control group (112.0 ± 23.72 pg/ml vs. 99.34 ± 15.15 pg/ml, t = 2.48, P = 0.015) . After co-culture with 721.221 cells, K562 cells and P815-Ab cells, the percentage of CD107a-expressing NK cells was significantly higher in NK cells from the alopecia areata group (9.53% ± 1.70%, 5.15% ± 1.35%, 6.50% ± 1.64%, respectively) than in those from the control group (5.00% ± 1.17%, 4.40% ± 1.09%, 5.13% ± 1.36%, respectively, all P < 0.05) . After the stimulation with P815-Ab cells, the alopecia areata group showed significantly decreased fluorescence intensity of CD16 + NK cells (151.10% ± 59.30%) compared with the control group (221.90% ± 93.56%, t = 4.31, P < 0.001) . After IL-18 stimulation, the percentage of CD107a-expressing NK cells significantly increased in the co-culture system of NK cells with 721.221 cells compared with the unstimulated co-culture system (14.47% ± 2.67% vs. 9.93% ± 1.94%, t = 6.00, P < 0.001) , while there was no significant difference between the IL-8-stimulated co-culture system of NK cells with K562 cells or P815-Ab cells and the unstimulated co-culture systems (both P > 0.05) . Conclusion:IL-18 could enhance NK cell activity in patients with alopecia areata, likely by promoting natural cytotoxicity receptor-mediated cytotoxicity.

T helper type 2 immune response in alopecia areata / 中华皮肤科杂志

Alopecia areata (AA) is a common inflammatory and non-scarring hair loss condition with unknown pathogenesis, and relapses are common in some patients. Evidence has demonstrated that allergy takes part in the early onset, severe condition, recurrence, and prolonged process in AA. Allergy to dust mites may be one of the reasons for refractory severe AA, especially in childhood, possibly due to the predominance of T helper type 2 (Th2) immune response. Desensitization can suppress the Th2 immune response, alter the immune balance, and reduce disease severity during AA relapses. In addition, high IgE levels may predict favorable efficacy of dupilumab in AA patients before treatment, while high interleukin-4 levels may predict the ineffectiveness of topical immunotherapy with diphenylcyclopropenone, which works by antagonizing Th1 immune response. Therefore, serum total IgE, specific IgE to dust mites, and interleukin-4 can be considered as biomarkers, revealing the predominance of Th2 immune response in AA patients. This article focuses on the relationship between allergy and AA, as well as the role of anti-allergic reactions and desensitization in the treatment of AA, aiming to provide ideas for precise and individualized treatment of AA.

Small-molecule targeted drugs and biological agents for alopecia areata / 中华皮肤科杂志

Traditional therapies for alopecia areata, especially moderate to severe alopecia areata and special types of alopecia areata, remain unsatisfactory. Compared with traditional therapies, small-molecule targeted drugs and biological agents have advantages of a more rapid onset of action and more marked efficacy, however, some patients may experience adverse reactions such as infections during treatment or relapses after drug withdrawal. Thus, their efficacy and safety still need to be further evaluated. This review summarizes research progress in small-molecule targeted drugs and biological agents in the treatment of alopecia areata.

Expression of peripheral interleukin-35 and its modulatory effect on regulatory T cell functions in patients with alopecia areata / 中华皮肤科杂志

Objective:To investigate changes in the peripheral interleukin-35 (IL-35) level in patients with alopecia areata, and to assess its modulatory effect on regulatory T (Treg) cell activities.Methods:Totally, 81 patients with alopecia areata (alopecia areata group) and 27 healthy volunteers (control group) were enrolled from Shanxi Provincial People′s Hospital between December 2019 and January 2021. Sera and peripheral blood mononuclear cells (PBMCs) were isolated. Enzyme-linked immunosorbent assay (ELISA) was performed to detect the serum IL-35 level, real-time fluorescence-based quantitative PCR to determine the mRNA expression of IL-35 subunits EBI3 and IL-12p35, and flow cytometry to determine the proportion of CD4 + CD25 + CD127 dim/- Treg cells. Sorted Treg cells were stimulated by recombinant human IL-35, ELISA was performed to detect levels of perforin and granzyme B in the culture supernatant, and real-time fluorescence-based quantitative PCR to determine the mRNA expression of EBI3, IL-12p35, and immune checkpoint molecules, such as programmed death protein 1 (PD-1) , T cell immunoglobulin and mucin protein-3 (Tim-3) , cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and lymphocyte activation gene-3 (LAG-3) in Treg cells. IL-35-stimulated or unstimulated Treg cells were co-cultured with autologous PBMCs, and cell counting kit-8 (CCK8) assay was conducted to assess cellular proliferative activity. Measurement data were compared between 2 groups by using t test, comparisons among multiple groups were carried out by using one-way analysis of variance, correlation analysis was carried out by using Pearson correlation analysis, and enumeration data were compared by using chi-square test. Results:Compared with the control group, the alopecia areata group showed significantly decreased IL-35 levels (90.10 ± 11.98 ng/L vs. 100.74 ± 28.71 ng/L, t= 2.71, P= 0.008) , mRNA expression of EBI3 and IL-12p35 in PBMCs (EBI3: 1.06 ± 0.15 vs. 1.25 ± 0.11, t= 6.09, P < 0.001; IL-12p35: 1.00 ± 0.15 vs. 1.38 ± 0.22, t= 10.16, P < 0.001) , and proportions of Treg cells (5.91% ± 1.17% vs. 6.85% ± 1.23%, t= 3.54, P= 0.001) . In the alopecia areata group, the proportion of Treg cells was positively correlated with the serum IL-35 level ( r= 0.25, P= 0.026) , and the mRNA expression of EBI3 and IL-12p35 in PBMCs ( r= 0.31, 0.24, P= 0.004, 0.032, respectively) . Compared with the control group, the unstimulated Treg cells from the alopecia areata group showed significantly decreased supernatant levels of perforin and granzyme B, mRNA expression of EBI3, IL-12p35 and immune checkpoint molecules ( P < 0.05 or 0.001) , as well as weakened inhibitory effect on the proliferative activity of PBMCs ( P= 0.013) . There was no significant difference in the level of perforin or granzyme B between the recombinant human IL-35-stimulated and unstimulated Treg cells from the patients with alopecia areata (both P > 0.05) . However, the mRNA expression of EBI3, IL-12p35 and immune checkpoint molecules was significantly higher in the IL-35-stimulated Treg cells than in the unstimulated Treg cells in the alopecia areata group ( P < 0.05 or 0.001) , and the inhibitory effect on the proliferative activity of PBMCs was also significantly enhanced in the IL-35-stimulated Treg cells compared with the unstimulated Treg cells ( P= 0.037) . Conclusion:The peripheral IL-35 level was significantly decreased in the patients with alopecia areata, which was closely associated with reduced activities of Treg cells, and IL-35 may be involved in the occurrence of alopecia areata.

Clinical remission of disseminated molluscum contagiosum infection in a patient with atopic dermatitis treated with dupilumab

Abstract Atopic dermatitis predisposes to skin infections, and on the other hand, some therapies used for atopic dermatitis may worsen viral infections whose lesions may be more diffuse and resistant to treatment. The authors present a patient with severe atopic dermatitis and disseminated molluscum contagiosum infection. The molluscum contagiosum did not clear with topical treatment, and it worsened her atopic dermatitis even more, so the authors started treatment with dupilumab. After two months, the patient's dermatitis went into clinical remission and there was resolution of the infection with no recurrence at the 12-month follow-up. Dupilumab is nowadays a promising treatment for severe atopic dermatitis. To our knowledge, only four reports of molluscum contagiosum during dupilumab therapy have been reported in the literature, with contrasting effects. According to the authors' experience, treatment with dupilumab appears to be a safe alternative for patients with severe atopic dermatitis who are also infected with molluscum contagiosum, as opposed to other treatments such as systemic corticosteroids or cyclosporine.

Evaluation of the level of serum Interleukins (IL-2, IL-4, IL-15 andIL-17) and its relationship with disease severity in patients with alopecia areata

Abstract 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.

Alopecia Areata pós-Covid-19: relação causal ou casual? / Alopecia Areata after COVID-19: causal or casual relationship?

A Covid-19, doença causadora de síndrome gripal e insuficiência respiratória aguda, vem demonstrando provocar danos a diversos outros órgãos e sistemas. Várias manifestações dermatológicas já foram descritas. Relatamos um quadro de alopecia areata (AA) desencadeada possivelmente pela Covid-19 em paciente que, apesar de ter seu RT-PCR para SARS-CoV-2 negativo, apresentou IgM reagente e sintomatologia clássica relacionada à doença. Acreditamos que a Covid-19 possa ter desencadeado resposta imunológica autoimune, com a consequente produção de interferons, que levou ao quadro de AA.

COVID-19, a disease that causes flu-like syndrome and acute respiratory failure, has been shown to cause damage to several other organs and systems. Several dermatological manifestations have been regular. We report a case of Alopecia Areata possibly triggered by COVID-19 in a patient who, despite his negative SARS-COV 2 RT- PCR, presented IgM reactor, in addition to classic symptoms related to the disease. We believe that a COVID-19 can trigger the autoimmune immune response with the consequent production of interferons that led to Alopecia areata.