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JEADV:BNT162b2疫苗接种SARS-CoV-2后重症寻常型天疱疮的发生

2022-01-31 医路坦克 MedSci原创

寻常型天疱疮(PV)是一种罕见而严重的皮肤粘膜自身免疫性疾病。在此,我们报告了首例患者,他在新冠肺炎接种BNT162b2mRNA疫苗后出现PV。

      寻常型天疱疮(PV)是一种罕见而严重的皮肤粘膜自身免疫性疾病。在PV中,针对皮肤桥粒蛋白(DSG)1和Dsg3的自身抗体的产生导致了以起泡和严重糜烂为特征的临床表型。据报道,包括遗传易感性、某些药物和恶性疾病在内的几个因素可以触发或加剧PV。在此,我们报告了首例患者,他在新冠肺炎接种BNT162b2mRNA疫苗后出现PV。

      一位40岁的亚裔女性患者在口腔粘膜、躯干和背部发生疼痛、无法愈合的糜烂后被转诊至我科(图1A-C)。患者的病史显示,第一次口腔损害发生在第一次使用BNT162b2 5天后的1月中旬。在患者接种第二针疫苗三天后,口腔病变严重恶化;此外,上半身出现水泡和糜烂。在接种疫苗之前,患者在其他方面是健康的,没有任何皮肤病病史,也没有任何药物治疗。由于临床表现可疑天疱疮,我们进行了皮肤和血液采样。皮损皮肤的组织学表现为下表皮层棘层松解,真皮内有致密的淋巴细胞浸润,并伴有丰富的浆细胞(图1D)。皮损周围皮肤的直接免疫荧光显示IgG在蜂窝状细胞间表皮模式中显著沉积(图1E)。最后,我们在患者血清中检测到高滴度的抗Dsg3和DSG1自身抗体(分别为974和124RE/mL)

      有了这些发现,我们确认了PV的临床疑似诊断,并开始了口服泼尼松(每公斤体重1毫克,最终逐渐减少)和硫唑嘌呤(100 mg/天)的免疫抑制治疗。这种方法停止了水泡的继续产生,减少了自身抗体的产生。患者目前正在我们诊所接受定期临床随访。

      BNT162b2疫苗是一种脂质纳米颗粒配制的核苷修饰RNA(ModRNA),编码SARSCoV-2全长刺突蛋白的灌注构象。注射后,常见的副作用,如局部发红、肿胀、疼痛或全身反应,如发烧、头痛、关节痛或腹泻,都是常见的症状。抗病毒疫苗接种后自身免疫疾病的临床表现很少见。不同的过程,如分子模仿、遗传易感者的炎症调节失调、表位扩散或旁观者激活,似乎参与了疫苗接种后自身免疫的发生。BNT162b2注射可激发强大的T和B细胞激活。接种BNT162b后,B细胞活性增强,浆细胞、记忆性B细胞数量和抗体水平迅速增加。接种BNT162b2后,个体产生了较强的IL-4,尽管关于BNT162b2免疫后IL-17和IL-21产生的数据尚不清楚,但BNT162b免疫后单个个体产生了较强的IL-4。尽管BNT162b2免疫后IL-17和IL-21的产生仍缺乏相关数据,但BNT162b2免疫后单个个体产生IL-4的能力较强。IL-17和IL-21与生发中心激活有关,与天疱疮等自身免疫性疾病密切相关,特别是在发病初期。然而,疫苗接种后的强烈抗体反应通常需要5天以上。在接种BNT162b1的患者中,14-21天后出现特异性抗体。在我们的患者中,接种BNT162b2很可能增强了她的T/B细胞反应,导致了意外的天疱疮发作。遗传易感性可能会促进这种副作用。

     即使我们不能确定BNT162b2与PV病变发生之间的直接病理联系,这两个事件之间也有明确的时间关系。这份报告并不打算引起公众对疫苗安全性的关注,但疫苗相关事件的发生需要记录,并可能有助于确定未来患者的风险概况,特别是那些具有亚临床自身抗体滴度的患者。

 

图1 接种SARS-CoV-2疫苗的天疱疮患者的临床表现和免疫组织学。(a和b)口腔粘膜广泛的疼痛糜烂;(C)上背部的腐蚀性环形红褐色病变;(D)皮损皮肤的组织学,有明显的棘皮病和强烈的真皮浸润;(E)皮损周围皮肤的直接免疫荧光表现为蜂窝状的细胞间表皮IgG沉积。

文献来源: Solimani F,  Mansour Y,  Didona D, Development of severe pemphigus vulgaris following SARS-CoV-2 vaccination with BNT162b2,J Eur Acad Dermatol Venereol 2021 Jun 25;

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    2022-05-27 cenghis
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    2022-11-07 hukaixun
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    2022-02-02 小刀医生

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