自身反应性T细胞与斑秃

斑秃的病因尚未完全清楚,但近年来多种研究表明,斑秃的发病与自身免疫有关,自身反应性T细胞在斑秃的发病中起着关键作用。综述自身反应性T细胞逃逸外周耐受、从外周血向毛囊迁移,及其介导斑秃发病的证据。研究斑秃自身反应性T细胞,有助于阐明斑秃的发病机制以及寻找有效及有针对性的治疗措施。     

Alopecia Areata in the Elderly: A 10-Year Retrospective Study

Background

Alopecia areata (AA) is an organ-specific autoimmune disease that typically occurs in young adults. AA in the elderly is relatively rare, thus little data have been reported.

Objective

This study aimed to understand the clinical characteristics of AA in the elderly.

Methods

We performed a 10-year retrospective study of AA in the elderly who visited our dermatologic clinic from January 2002 to December 2011. A clinical review of medical records and telephone interviews were performed by two dermatologists.

Results

Among 1,761 patients with newly diagnosed AA, 61 (3.5%) were older than 60 years at the first visit. Among those who completed a telephone interview, 74.3% (26/35) had less than 50% of scalp-localized hair loss. There was no association between the extent of AA and hair graying (p=0.679). Favorable therapeutic response was observed in 62.9% (22/35) of cases.

Conclusion

AA in the elderly shows mild disease severity and favorable treatment response. There is no association between graying and the extent of AA. However, the influence of aging on the pathogenesis of AA in the elderly deserves further investigation.     

Trichostasis spinulosa of the scalp mimicking Alopecia Areata black dots

Alopecia areata is a common autoimmune disorder that leads to nonscarring hair loss. Black dots, also called comedo-like cadaver hairs, can be found in almost 50% of alopecia areata patients and indicate disease activity. Trichostasis spinulosa is a follicular disorder resulting from the retention of numerous hairs surrounded by a keratinous sheath in dilated follicles. Trichostasis spinulosa is a relatively common but underdiagnosed disorder of hair follicles. Here, we describe a man with alopecia areata of the eyebrows, androgenetic alopecia and trichostasis spinulosa at the vertex and show how dermoscopy can be useful in distinguishing black dots from Trichostasis spinulosa lesions.     

斑秃655例伴发疾病分析

目的探讨斑秃发病的临床特点及伴发疾病分析。方法收集本科门诊2006年1月-2008年5月确诊的斑秃患者,以调查表的形式收集患者临床资料及伴发疾病情况,包括斑秃发病年龄、病程、严重程度、家族史和复发情况等,用SPSS13.0软件分析。结果 655例斑秃患者,男320例,女335例,平均年龄(38.4±12.4)岁,平均病程(14.8±35.7)个月,88例(13.44%)为全秃/普秃,84例(12.82%)家族史阳性,195例(29.77%)斑秃反复发作。655例患者中,190例(29.01%)除斑秃外,还伴发至少1种过敏性疾病或自身免疫性疾病,仅伴过敏性疾病者123例(18.78%)。未发现伴发疾病与性别、发病年龄、病程、斑秃类型、既往史及家族史相关联(P>0.05)。全秃/普秃更易伴发过敏性疾病,包括湿疹、荨麻疹、哮喘和药物过敏(P=0.004),与无伴发过敏性疾病的斑秃患者相比,伴发者发病更早(P=0.033)。结论斑秃与伴发的其他疾病可能有着相同的遗传学、免疫学基础,不同的伴发疾病可能对斑秃的发生、发展和预后产生不同的影响。     

二苯环丙烯酮治疗斑秃16例疗效观察

目的观察斑秃患者局部外用二苯环丙烯酮(DPCP)治疗的临床疗效。方法应用DPCP治疗16例斑秃患者,2%DPCP外搽秃发区致敏,1周后用0.001%DPCP外搽患者头皮,每周1次,并据患者反应增加浓度观察其治疗反应及副作用,并与局部外用米诺地尔酊2次/d进行对照。结果治疗组坚持治疗的11例患者中,8例出现终毛生长,有效率为72.73%,达到良好反应的中位时间为(9.07±3.96)月,停止治疗后复发率为25.00%,12.50%患者出现较严重副作用。对照组13例坚持治疗,4例患者出现终毛生长,有效率30.77%,复发率为25.00%。治疗组疗效明显优于对照组(P<0.05)。结论 DPCP治疗斑秃有效率高,安全性相对较好,是值得推荐的一种有效治疗方法。     

Preferential Recognition of Hydroxyl Radical-Modified Superoxide Dismutase by Circulating Autoantibodies in Patients with Alopecia Areata

Background

Alopecia areata (AA) is a common form of localized, non-scarring hair loss. The cause of AA is unknown but reports suggest an autoimmune etiology, where oxygen free radicals play an important role.

Objective

The aim of this study was to investigate the role of a hydroxyl radicals (·OH)-modified antioxidant enzyme, superoxide dismutase (SOD), in AA autoimmunity.

Methods

SOD was modified by ·OH radicals. Binding characteristics of autoantibodies in AA patients (n=26) against ·OH-modified SOD (·OH-SOD) were evaluated by immunoassays and the results were compared with those of healthy, age-matched controls (n=30). The effects of ·OH radicals on immunoglobulin G (IgG) isolated from AA patients were studied.

Results

Highly specific binding to ·OH-SOD was observed in 32% of the samples of patient sera, whereas normal human sera showed negligible binding with either antigen. Competitive inhibition immunoassays reiterated the results from direct binding. Protein-A-purified IgG from AA patients (AA-IgG) also showed strong binding to ·OH-SOD as compared to IgG from normal human controls (p<0.001). In addition, AA-IgG from patients with alopecia universalis recognized ·OH-SOD to a greater extent than did AA-IgG from patients with the patchy, persistent type of alopecia. Furthermore, sera from AA patients had lower levels of SOD activity as compared to control sera.

Conclusion

This is the first report showing an association between ·OH-modified SOD and AA. These novel results demonstrate that ·OH radical-mediated changes in SOD present unique neo-epitopes that might contribute to antigen-driven antibody induction in AA.     

Clinical Relevance for Serum Cold-Inducible RNA-Binding Protein Level in Alopecia Areata

BackgroundAlopecia areata (AA), a chronic, relapsing hair-loss disorder, is considered to be a T-cell-mediated autoimmune disease. Cold-inducible RNA-binding protein (CIRP) belongs to a family of cold-shock proteins that respond to cold stress, and has been identified as a damage-associated molecular pattern (DAMP) molecule that triggers the inflammatory response. Recent studies have shown that high-mobility group box 1, another DAMP molecule, is elevated in serum and scalp tissue of AA patients, suggesting a relationship between DAMP molecules and the pathogenesis of AA.ObjectiveTo investigate the clinical significance of serum CIRP levels in AA.MethodsThe serum levels of CIRP were compared between 68 patients with AA and 20 healthy controls. Additionally, the correlation between CIRP level and various clinical parameters was evaluated.ResultsThe serum CIRP levels were significantly higher in AA patients compared to healthy subjects. Moreover, there was an association between the serum CIRP level and clinical characteristics, such as disease duration and disease activity. However, there was no significant difference in the serum CIRP level among the clinical types of AA (AA multiplex, alopecia totalis, and alopecia universalis).ConclusionThese results suggest that CIRP may play a significant role in the pathogenesis of AA and could be a potential biologic marker for monitoring the disease activity of AA.     

白癜风发病与自身免疫性甲状腺病的相关性探讨

目的探讨白癜风与自身免疫性甲状腺病(AITD)的发生是否存在相关性。方法用化学发光分析法测定38例白癜风患者和35名正常人群的甲状腺功能(包括抗甲状腺球蛋白抗体和抗甲状腺过氧化物酶抗体),比较白癜风患者和正常对照组间甲状腺自身抗体阳性率,同时比较甲状腺自身抗体阳性的白癜风患者与甲状腺自身抗体阴性的白癜风患者间AITD患病率。结果白癜风患者T3和T4与正常对照组比较差异无显著性(P>0.05),而白癜风患者FT3和FT4与正常对照组比较差异均有显著性(P<0.05)。白癜风患者血清TSH与正常对照组比较差异有显著性(P<0.01)。白癜风患者甲状腺自身抗体阳性率与正常对照组比较均有增高趋势(P<0.05)。甲状腺自身抗体阳性的白癜风患者AITD患病率(41.18%)与甲状腺自身抗体阴性的白癜风患者(9.52%)间比较明显增高(P<0.05)。结论白癜风的发病与甲状腺功能的改变和自身免疫有着密切的联系。     

补肾养血生发丸治疗斑秃56例疗效观察

目的：探讨补肾养血生发丸治疗斑秃的临床疗效。方法：对108例斑秃患随意分为两组;治疗组为补肾养血生发丸口服,外搽补肾活血生发精,对照组口服维生素E,外搽1％敏乐啶溶液,在治疗后2个疗程,观察临床疗效。结果：治疗组56例中,痊愈42例,显效11例,无效3例,总有效(痊愈 显效)率为94．6％,对照组52例中,痊愈25例,显效14例,无效13例,总有效率75％,两组间有效率有非常显性差异(x^2＝6．83,P＜0．01)。结论：口服补肾养血生发丸与外搽补肾活血生发精治疗斑秃有明显疗效。     

Differences in Comorbidity Profiles between Early-Onset and Late-Onset Alopecia Areata Patients: A Retrospective Study of 871 Korean Patients

Background

Alopecia areata (AA) is a common dermatologic condition with a broad spectrum of clinical features and age of onset, classically characterized by nonscarring patches of hair loss. In the past, early-onset (before adolescence) AA has been associated with various autoimmune diseases, especially atopic diseases and lupus erythematosus and demonstrates a worse prognosis compared with late onset AA.

Objective

To evaluate the differences in the comorbidity profile of AA with regard to age at onset.

Methods

We completed a retrospective study of 871 Korean AA patients seen at our department within the last 10 years. After these patients were subdivided according to onset before or after age 13 years, the two groups were compared on the basis of their comorbid disorders, family history of AA, and hematologic test results.

Results

Our results demonstrate that significantly more patients in the early-onset group had a personal history of atopic dermatitis or family history of AA. These findings are consistent with previous reports associating early-onset AA with autoimmune diseases and a family history of AA in different ethnic populations. Most of the serologic test values showed no significant differences between the groups and the results were considerably affected by age.

Conclusion

This study is significant because it is a large group study in Korean AA patients, and Korean AA patients with an onset age before adolescence show similar clinical manifestations to other ethnic populations.     

斑秃发病机制的实验研究进展

斑秃是一种发生于毛囊的非瘢痕性、炎症性疾病,尽管临床无明显炎症表现,但组织病理学检查显示,生长期毛囊有淋巴细胞浸润和炎症介质增多,临床用免疫调节或抑制剂治疗有效。斑秃发病与自身免疫有关,是炎症细胞介导的、器官特异性疾病。啮齿类动物有自发脱发现象,其发病机制与人类斑秃相似,文中就啮齿类动物(C3H/HeJ小鼠和DEBR鼠)的秃发特征和发病机制研究现状作一综述。     

Comparison of High-Dose Corticosteroid Pulse Therapy and Combination Therapy Using Oral Cyclosporine with Low-Dose Corticosteroid in Severe Alopecia Areata

BackgroundSevere alopecia areata (AA) is resistant to conventional treatment. Although systemic oral corticosteroids are an effective treatment for patients with severe AA, those drugs have many adverse effects. Corticosteroid pulse therapy has been introduced to increase therapeutic effects and reduce adverse effects. However, the treatment modality in severe AA is still controversial.ObjectiveTo evaluate the effectiveness of corticosteroid pulse therapy in patients with severe AA compared with treatment with oral cyclosporine with corticosteroid.MethodsA total of 82 patients with severe AA were treated with corticosteroid pulse therapy, and 60 patients were treated with oral cyclosporine with corticosteroid. Both groups were retrospectively evaluated for therapeutic efficacy according to AA type and disease duration.ResultsIn 82 patients treated with corticosteroid pulse therapy, 53 (64.6%) were good responders (>50% hair regrowth). Patients with the plurifocal (PF) type of AA and those with a short disease duration (≤3 months) showed better responses. In 60 patients treated with oral cyclosporine with corticosteroid, 30 (50.0%) patients showed a good response. The AA type or disease duration, however, did not significantly affect the response to treatment.ConclusionCorticosteroid pulse therapy may be a better treatment option than combination therapy in severe AA patients with the PF type.     

Alopecia universalis during treatment with leflunomide and adalimumab - Case report

Alopecia areata is a non-scarring form of alopecia that can be localized orwidespread. Its etiology is unknown, but immunological factors are implicated in itspathogenesis. With the more frequent use of anti TNFα biologic drugs, some alopeciaareata cases during their use have been described. We report a case of universalalopecia in a patient with rheumatoid arthritis while using adalimumab andleflunomide.     

斑秃患者血浆和皮损中降钙素基因相关肽、血管活性肠肽的研究

目的 探讨降钙素基因相关肽(CGRP)和血管活性肠肽(VIP)在斑秃发病中的作用。方法 利用放射免疫分析法检测30例斑秃患者和20例正常人血浆中的CGRP和VIP水平,利用免疫组化方法检测21例斑秃患者皮损和16例正常人头皮中的CGRP和VIP表达情况。结果 ①斑秃活动期患者血浆中的CGRP水平为(142.63±67.95)pg/mL,低于稳定期(197.33±67.15)pg/mL和正常人(188.40±72.95)pg/mL,差异均有显著性。②斑秃活动期血浆中的VIP水平为(105.94±55.42)pg/mL,低于斑秃稳定期(156.86±47.37)pg/mL和正常人(176.44±84.70)pg/mL,差异均有显著性。③CGRP和VIP在斑秃皮损及其周围的表达明显低于正常人,差异有显著性。结论 CGRP和VIP在斑秃发病中起一定的作用。     

儿童斑秃患者外周血Th17及IL-17水平研究

目的研究儿童斑秃患者外周血Th17细胞及白细胞介素(IL)-17的变化,探讨其在儿童斑秃患者发病中的作用。方法采用流式细胞术检测儿童斑秃患者外周血Th17细胞的比例,采用酶联免疫吸附测定法(ELISA)测定培养上清液中IL-17表达水平,以健康儿童作为对照。结果儿童斑秃患者外周血与健康儿童比较,外周血Th17细胞比例、IL-17水平增高(P<0.05);重度儿童斑秃患者与轻度儿童斑秃患者比较,外周血Th17细胞比例及IL-17水平增高(P<0.05);稳定期儿童斑秃患者与活动期儿童斑秃患者外周血比较,外周血Th17细胞比例、IL-17水平增高(P<0.05)。结论 Th17细胞及IL-17可能在儿童斑秃的发生及发展过程中发挥重要作用。     

Combination Therapy with Cyclosporine and Psoralen Plus Ultraviolet A in the Patients with Severe Alopecia Areata: A Retrospective Study with a Self-Controlled Design

Background

Alopecia areata (AA) is believed to be an organ-specific autoimmune disease in which a mononuclear cell infiltrate develops in and around anagen hair follicles. There is no definitive therapy for AA.

Objective

We sought to determine whether the combination therapy of cyclosporine and psoralen plus ultraviolet A (PUVA) could be an effective treatment for severe AA.

Methods

A total of 41 patients with severe AA were treated with oral cyclosporine and topical PUVA. Cyclosporine was given at an initial daily dose of 200 mg for adult and 100 mg for children for periods of up to 16 weeks. Eight-methoxypsoralen (Methoxsalen) was applied topically 20 minutes prior to ultraviolet A (UVA) exposure, and the patients were irradiated with UVA twice a week for 16 weeks.

Results

Of the total 41 patients, 2 (7.3%) patients were lost to follow-up, and 1 (2.4%) patient discontinued the treatment due to abdominal discomfort. Six (14.6%) patients were treated for less than 12 weeks. Of remaining 32 patients, 3 (9.4%) showed excellent response, 3 (9.4%) showed good response, 12 (37.5%) showed fair response, and 14 (43.7%) showed poor response.

Conclusion

Although limited by its uncontrolled character, this study shows that the combination therapy with cyclosporine and PUVA may be an additional choice for severe and recalcitrant AA.     

Detection of Antibodies to Human Melanoma Cells in Vitiligo and Alopecia Areata by Western Blot Analysis

Antibody reactivity to human melanoma cells (SK-Mel-23) was investigated in 48 patients with vitiligo, 14 with alopecia areata (AA), and 35 normal control individuals by Western blot analysis. Antibodies to SK-Mel-23 were found in 44 (92%) of the patients with vitiligo, in 7 (50%) of the patients with AA, and in 14 (40%) of the normal control individuals. Significant differences between patients with vitiligo and normal controls were found in the incidence and distribution of antibodies, but no significant differences were found between patients with AA and normal controls. The antibodies were predominantly directed to one or more antigens of approximately 110 KD, 103 KD, 88 KD, 70 KD, 56 KD, 46 DK, or 41 KD. The most common responses were to 110 KD, 88KD, and 70 KD antigens. These antibodies were present in 60%, 60%, and 73% of the patients with vitiligo; 7%, 14% and 35% of the patients with AA; and 11%, 11% and 40% of normal control individuals, respectively. There were no statistical differences in the incidence of antibodies to pigment cells between segmental and non-segmental vitiligo. These findings suggest that autoreactivity to pigment cells occurs mostly in patients with vitiligo and might be a secondary immune reaction to destroyed pigment cells.     

A Comparative Study of Oral Cyclosporine and Betamethasone Minipulse Therapy in the Treatment of Alopecia Areata

BackgroundVarious systemic agents have been assessed for the treatment of alopecia areata (AA); however, there is a paucity of comparative studies.ObjectiveTo assess and compare cyclosporine and betamethasone minipulse therapy as treatments for AA with regard to effectiveness and safety.MethodsData were collected from 88 patients who received at least 3 months of oral cyclosporine (n=51) or betamethasone minipulse therapy (n=37) for AA. Patients with ≥50% of terminal hair regrowth in the alopecic area were considered responders.ResultsThe responder of the cyclosporine group was 54.9% and that of the betamethasone minipulse group was 37.8%. In the cyclosporine group, patients with mild AA were found to respond better to the treatment. Based on the patient self-assessments, 70.6% of patients in the cyclosporine group and 43.2% of patients in the betamethasone minipulse group rated their hair regrowth as excellent or good. Side effects were less frequent in the cyclosporine group.ConclusionOral cyclosporine appeared to be superior to betamethasone minipulse therapy in terms of treatment effectiveness and safety.     

Relationship of Hair Regrowth Pattern in Alopecia Areata Patches According to DIMT Classification with Treatment Modalities and Patch Size: A Retrospective Cross-Sectional Analysis

BackgroundThe morphology of hair regrowth in alopecia areata (AA) patches could be classified into four types, namely diffuse, irregular, marginal, and targetoid patterns, according to the DIMT classification. However, factors affecting hair regrowth patterns have not been investigated.ObjectiveWe investigated whether the DIMT-classified hair regrowth patterns of AA patches are associated with treatment modality and patch size.MethodsWe conducted a retrospective, cross-sectional study of 152 AA patches with hair regrowth.ResultsThe associations between the diffuse pattern and patch size >2 cm (p=0.006; odds ratio [OR]: 0.36, 95% confidence interval [CI]: 0.17~0.74), between the irregular pattern and triamcinolone acetonide intralesional injection (p<0.001; OR: 274.87, 95% CI: 25.75~2,933.56), between the marginal pattern and systemic and topical corticosteroid (p=0.018; OR: 4.89, 95% CI: 1.31~18.27), and between the targetoid pattern and patch size >2 cm (p=0.028; OR: 2.50, 95% CI: 1.10~5.68) were statistically significant.ConclusionTreatment modalities and patch size are the factors affecting hair regrowth patterns in AA patches.     

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

BackgroundWe found microRNA (miR)-1246 to be significantly differentially expressed between severe active alopecia areata (AA) patients and healthy individuals.ObjectiveTo explore the role and mechanism of miR-1246 in severe AA.MethodsExpression 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.ResultsmiR-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.ConclusionmiR-1246 can inhibit NFAT signaling and Th17 cell activation, which may be beneficial in the severe AA treatment.