斑秃（3）-读书报告

读专著，学专业英语！

Prognosis in alopecia areata isvariable and not very predictable in the individual patient. Nevertheless, it has been observed that theprognosis tends to be good in patients who have experienced hair growth withlonglasting remissions between episodes. Spontaneous remission can be expectedin 34–50% of patients within 1 year, although almost all will experience morethan one episode of the disease. Contrariwise,those who have had persistent hair loss or brief or incomplete remissions havea poor prognosis. Severity of alopecia areata at time of first consultation andresponse to therapy is an important prognostic factor.The outlook is particularly poor in those patients with onset of the diseasebefore puberty, those with a family history of the disease (present in 25% ofcases), and those with alopecia totalis and alopecia universalis.7 Atopic patients appear to suffer a more severe formof alopecia areata.

斑秃患者的预后是可变的，且在个别患者中不可预测。然而，在那些发作间歇期有头发生长并伴有持续缓解的患者，预后较好。虽然几乎所有的患者都会经历不止1次的发作，仍可预测34%-50%的患者1年内可达自然缓解。反之，那些有永久性脱发或有短的或不完全缓解的患者预后较差。首次就诊时斑秃的严重程度和对治疗的反应是预后的重要因素。在青春期前期发病并伴有家族史（25%的病例存在家族史）的患者和全秃、普秃的患者预后尤其差。特应性患者的斑秃显得更为严重。

Pathogenesis andhistological features

发病机制和组织学特征

Experimentalstudies have shown that alopecia areata is basically an organ-specificautoimmune disease thought to result from a collapse of hair follicle immuneprivilege, driven by cellular immunity with autoantibody production representinga secondary phenomenon. Autoantibodiesto a diverse range of antigens including smooth muscle cells, gastric parietalcells, thyroid cells, and components of anagen hair follicles have beendescribed.

实验研究表明，斑秃本质上是一种器官特异性自身免疫性疾病，是由于毛囊免疫耐受失效，细胞免疫驱动且继发自身抗体产生所致。针对多种抗原包括平滑肌细胞、胃壁细胞、甲状腺细胞以及毛囊抗原成分的自身抗体已被描述。

It isunknown whether induction of the disease results from exposure to exogenous orendogenous antigens and whether it represents a consequence of an immunereaction to normal or aberrant epitopes. However, recent research suggests thatthe pathogenesis involves at least four events:

• failureof the anagen hair follicle to maintain its privileged immunity (the inner rootsheath and hair matrix do not express, or express very low level of, majorhistocompatibility complex class Ia antigens and maintains an active NK cellsuppression) resulting in exposure of epitopes, which initiate an immuneresponse。

• antigenpresentation, activation, and response of the lymphocyte to antigen-presentingcells,

• migrationof activated inflammatory cells and infiltration of hair follicles,

• damage tothe hair follicle by the inflammatory cell infiltrate.

目前还不清楚该病是否因外源性或内源性抗原的暴露所致，以及本病是否代表了正常或异常抗原表位的免疫反应的结果。然而，最近的研究表明，发病机制包括至少四个方面：

• 生长期毛囊不能维持其免疫耐受（内根鞘和毛基质不表达，或表达极低水平的主要组织相容性复合体Ia抗原并维持活跃的NK细胞抑制）引起抗原表位暴露，从而启动免疫应答。

• 抗原呈递、淋巴细胞活化和对抗原呈递细胞的反应

• 活化的炎症细胞迁移和毛囊浸润

• 炎症细胞浸润损伤了毛囊

It has been proposed that neurotrophins playa role in the pathogenesis of the disease. These represent a family ofstructurally and functionally related proteins that are important not only inthe development and maintenance of cutaneous innervation but also in control ofhair follicle development and cycling. Since neurotrophins and their receptorsare differentially expressed in subsets of immune cells in alopecia areata, arole for these proteins in the pathogenesis appears likely.

现已提出，神经营养因子在疾病的发病机制中起一定的作用。神经营养因子代表了一系列结构和功能相关的蛋白质，它们不仅对皮肤神经的发育和维持提供支持，而且在调控毛囊发育和生长周期中也起着重要作用。由于神经营养因子及其受体在斑秃患者的免疫细胞亚群中的表达不同，故这些蛋白可能在发病机制中起一定的作用。

The increased frequency of alopecia areata ingenetically related individuals suggests that there is a genetic link to thedisease. Amongst the general population the condition does not display amendelian pattern of expression since the resultingphenotype demonstrates variable degrees of hair loss. It has been proposed thatexpression of alopecia areata involves a complex interaction of multiple genes,in which major genes control susceptibility to the disease while other minorones modify the phenotype.

有家族史的个体发生斑秃的几率增加提示本病与遗传有关。在普通人群中，本病的表型为不同程度的脱发，不符合孟德尔遗传模式。有人提出，斑秃是多基因相互作用的结果，其中主要的基因控制对本病的易感性，其他次要基因决定疾病的表型。

Manyillnesses with an autoimmune basis have been associated with specific humanleukocytic antigens (HLA). Alopecia areata has been studied in association withboth HLA class I and class II. The most relevant associations have been foundwith the HLA class II antigens (HLA-DR, -DQ, -DP). The molecular basis of thisgenetic association is supported by the fact that HLA binds and presentspeptides derived from self and foreign protein antigens to the immune systemfor recognition and activation. More than 80% of all cases evaluated in onestudy were positive for the antigen DQB1*03 (DQ3), suggesting that this antigenis a marker for susceptibility. Furthermore, in patients with alopecia totalisand universalis, the frequency of the antigens DRB1*0401 and DBQ1*0301 (DR4 andDQ7) is significantly increased. HLA-DR5 has been linked to the early-onset and severe form of alopeciaareata.

许多具有自身免疫基础的疾病与人类白细胞抗原（HLA）相关。斑秃已被研究证实与HLA I类和II类抗原均相关。已发现与HLA II类抗原（HLA-DR,-DQ,-DP）关联性最强。这种遗传关联的分子基础可被HLA结合并呈递来自自身和外源性蛋白抗原的肽类供免疫系统识别和激活的事实支持的。在一项研究中超过80%的病例DQB1 * 03（DQ3）抗原阳性，表明该抗原可作为易感性的标记抗原。此外，在全秃和普秃患者中，DRB1 0401和DBQ1 * 0301（DR4和DQ7）抗原的几率明显增加。HLA-DR5已被证实与早发和严重的斑秃相关。

Theeffect of stress on the pathogenesis is unclear and controversial, although ithasbeen suggested that it can trigger the disease. It has been observed that substance P and nerve growth factor could beacting as key mediators of stress-induced hair growth-inhibitory effects, throughkeratinocyte apoptosis, inhibition of hair follicle proliferation, and catageninduction.  On theother hand, stress in relation to alopecia areata was studied in a Turkishhospital after two consecutive earthquakes. The number of patients admittedwith alopecia areata before and after the earthquakes did not increase,suggesting that stress per se is not a primary trigger.

应激在发病机制中的作用并不清楚且存在争议，虽然已有研究证实应激可诱发斑秃。有研究观察发现P物质和神经生长因子可以作为应激诱导毛发生长抑制效应的主要介质，通过角质形成细胞凋亡，抑制毛囊增殖，诱导退行期。另一方面，土耳其的一家医院曾研究连续两次地震后应激与斑秃的关系。在地震前后，斑秃患者的数量并未增加，证实了应激本身并不是主要诱因。

–––––––––––––––––––––––––––––––––––

未完待续 （浙江省人民医院皮肤科 李亚丽博士译）2017-11-14