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第一剂 COVID-19 疫苗可能会引发天疱疮和大疱性类天疱疮：因此是否禁用第二剂？

J. Eur. Acad. Dermatol. Venereol.

Pub Date  : 2021-06-25

DOI : 10.1111/jdv.17472

G. Damiani, A. Pacifico, F. Pelloni, M. Iorizzo

亲爱的 编辑，

在 COVID-19 大流行期间，受自身免疫性大疱病 (AIBD) 影响的免疫抑制患者的管理成为医疗保健系统特别关注的问题；传播可靠和更新的信息成为指导医生和更普遍的医疗保健政策的强制性要求。1, 2此外，鼓励 AIBD 患者利用远程皮肤病咨询而不是面对面咨询；此外，鼓励他们接种 COVID-19 疫苗，最好是在缓解期或至少在免疫抑制较低的情况下。3、4迄今为止，关于 COVID 疫苗对 AIBD 影响的数据很少。我们介绍了 5 例（来自 4 个不同中心）大疱性类天疱疮 (BP) - 分别是寻常型天疱疮 (PV) - 均通过临床、免疫病理学/血清学发现证实，其中患者在大疱缓解期间接受了 COVID 疫苗接种疾病并随后经历了疾病发作（表 1）。

表 1.受 AIBD 影响的患者的数据

性别/年龄人工智能BD以前的 AIBD 药物疫苗（2剂）新药用于治疗抗 SARS-CoV-2 S1-RBD IgG >50 UI/L1F/75BP口服泼尼松摩登纳口服泼尼松是的2米/40光伏利妥昔单抗摩登纳

口服泼尼松

吗替麦考酚酯

是的3M/84BP

口服泼尼松

硫唑嘌呤

摩登纳口服泼尼松**治疗仅在第 2 次给药后开始。

是的4F/82BP

口服泼尼松

吗替麦考酚酯

辉瑞口服泼尼松是的5米/80光伏

口服泼尼松

吗替麦考酚酯

辉瑞口服泼尼松是的

*治疗仅在第 2 次给药后开始。

案例1。一名 63 岁女性，大疱性类天疱疮 (BP) 在口服泼尼松治疗 6 个月后临床缓解，接种第一剂 Moderna mRNA-1273 疫苗，3 天后，她的疾病突然发作：后者接种后第1天开始出现全身红斑，第3天后躯干出现数个水泡。诊断是在远程医疗咨询中做出的，并开了口服泼尼松。28 天后，患者接受了第二剂疫苗，没有出现疾病发作，也没有发生注射部位反应。

案例2。一名 40 岁男性患有寻常型天疱疮 (PV)，自利妥昔单抗治疗一年后开始缓解，由于 PV 耀斑，在第一剂 Moderna mRNA-1273 疫苗后 3 天引起了我们的注意。他的背部和上肢出现数个水泡（图 1），并开始使用吗替麦考酚酯和口服泼尼松进行治疗。28 天后，他接受了第二剂疫苗：他仅在注射部位感到疼痛 2 天。



图。1

在图形查看器中打开微软幻灯片软件

2 号患者在第一剂 Moderna mRNA-1273 疫苗后出现 PV 耀斑

案例3。一名 84 岁男性，在口服泼尼松和硫唑嘌呤治疗 4 年后血压有所缓解，他接种了第一剂 Moderna mRNA-1273 疫苗。2 周后，他开始在躯干上出现轻微的水疱病变，认为不需要全身免疫抑制治疗。28 天后，给予患者第二剂；病变的恶化变得更加普遍，也涉及口腔。开始口服泼尼松治疗。

案例4。一位 82 岁女性，在口服泼尼松和霉酚酸酯治疗 3 年后血压缓解，接受了辉瑞 mRNABNT162b2 疫苗的第一剂注射。3 天后，患者出现中度血压升高，手臂和腿部出现小水泡。患者住在疗养院，那里只能进行远程皮肤科会诊。处方口服泼尼松，21 天后服用第二剂。没有进一步的血压升高，也没有发生注射部位反应。

案例5。一名有 PV 病史的 80 岁男性在口服泼尼松和吗替麦考酚酯治疗后 1 年之前缓解，在第一剂 mRNABNT162b2 疫苗后 3 天出现了耀斑。由于背部有严重的水泡，他在远程皮肤科会诊中被看到，并接受了口服泼尼松治疗。21 天后，患者能够完成第二剂辉瑞 mRNABNT162b2 疫苗接种。没有进一步的血压升高，也没有发生注射部位反应。

尽管持续使用免疫抑制剂进行治疗，但所有患者在第二次接种后 1 个月都产生了针对 SARS-CoV-2 S1 受体结合域 (RBD) 的 IgG 抗体（>150 UI），这支持了疫苗接种对所有患者有效的假设提出的案例。

这些轶事数据表明两种 mRNA 疫苗都可能引发 AIBD 患者的复发。疫苗对 AIBD 患者很重要，因为后者的特点是对皮肤粘膜屏障感染的脆弱性5：建议完成疫苗接种，并在需要时对患者进行治疗。然而，需要关于免疫抑制剂对 IgG 抗体滴度的短期和长期影响的数据。AIBD 患者中 IgG S1-RBD 的持续存在也是一个值得关注的问题；这应该鼓励皮肤科医生监测抗 COVID-19 的免疫力。



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英文标题摘要

The first dose of COVID-19 vaccine may trigger pemphigus and bullous pemphigoid flares: is the second dose therefore contraindicated?

Dear Editor,

During the COVID-19 pandemics, the management of immunosuppressed patients, those affected by autoimmune bullous diseases (AIBDs), became a matter of particular concern for healthcare systems; dissemination of sound and updated information became mandatory to orient physicians and more generally healthcare policy.1, 2 Furthermore, AIBDs patients were encouraged to take advantage from teledermatological rather than in-person consultations; also, they were encouraged to undergo COVID-19 vaccination, preferably during remission periods or at least while under low immunosuppression.3, 4 To date, data regarding the effect of COVID vaccines on AIBDs are scanty. We present 5 cases (from 4 different centres) of bullous pemphigoid (BP) – respectively of pemphigus vulgaris (PV) – all confirmed by clinical, immunopathologic/serological findings, where the patients had undergone COVID vaccination during a period of remission of their bullous disease and have subsequently experienced a disease flare (Table 1).

Table 1. Data of AIBD-affected patients

Sex/ageAIBDPrevious medications for AIBDsVaccine (2 doses)New medications for flare upAnti-SARS-CoV-2 S1-RBD IgG >50 UI/L1F/75BPOral prednisoneModernaOral prednisoneYes2M/40PVRituximabModerna

Oral prednisone

Mycophenolate mofetil

Yes3M/84BP

Oral prednisone

Azathioprine

ModernaOral prednisone** Treatment started only after the 2nd dose.

Yes4F/82BP

Oral prednisone

Mycophenolate mofetil

PfizerOral prednisoneYes5M/80PV

Oral prednisone

Mycophenolate mofetil

PfizerOral prednisoneYes

* Treatment started only after the 2nd dose.

Case 1. A 63-year-old female with bullous pemphigoid (BP) in clinical remission since 6 months after oral prednisone treatment was administered the first dose of Moderna mRNA-1273 vaccine, and 3 days later, she experienced a flare of her disease: the latter started with a generalized erythema 1 day after the vaccination, and on the third day, several blisters appeared on the trunk. The diagnosis was made in a telemedical consultation and oral prednisone was prescribed. 28 days later, the patient was given the second dose of the vaccine, and no disease flares and no injection site reactions took place.

Case 2. A 40-year-old male, with pemphigus vulgaris (PV) in remission since one year after rituximab therapy, came to our attention 3 days after the first dose of the Moderna mRNA-1273 vaccine because of a PV flare. He presented with several blisters on the back and on the upper limbs (Fig. 1) and started a therapy with mycophenolate mofetil and oral prednisone. After 28 days, he was given the second dose of the vaccine: he experienced only pain on the injection site for 2 days.



Fig. 1

Open in figure viewerPowerPoint

Patient number 2 showing a flare of PV after the 1st dose of Moderna mRNA-1273 vaccine

Case 3. A 84-year-old male with BP in remission since 4 years after oral prednisone and azathioprine treatment was administered the first dose of the Moderna mRNA-1273 vaccine. After 2 weeks, he started showing mild blistering lesions on the trunk, which were deemed not to require systemic immunosuppressive treatment. 28 days later, the patient was given the second dose; a worsening of the lesions which became more widespread, involving also the oral cavity, took place. A treatment with oral prednisone was started.

Case 4. A 82-year-old female with BP in remission since 3 years after oral prednisone and mycophenolate mofetil treatment was given the first dose of the Pfizer mRNABNT162b2 vaccine. 3 days later, the patient experienced a moderate BP flare in the form of small blisters on the arms and legs. The patient lived in a nursing home where only teledermatological consultations were possible. Oral prednisone was prescribed, and the second dose was administered 21 days later. No further BP flares and no injection site reactions occurred.

Case 5. A 80-year-old male with a history of PV remitted before 1 year after oral prednisone and mycophenolate mofetil treatment experienced a flare 3 days after the first dose of the mRNABNT162b2 vaccine. He was seen in a teledermatological consultation because of severe blisters on the back, and he was treated with oral prednisone. After 21 days, the patient was able to complete the second dose of Pfizer mRNABNT162b2 vaccination. No further BP flares and no injection site reactions occurred.

Despite the ongoing treatment with immunosuppressants, all patients developed IgG antibodies against the SARS-CoV-2 S1-receptor binding domain (RBD) (>150 UI) 1 month after the second dose, which supports the assumption that the vaccination was effective in all cases presented.

These anecdotal data suggest that both mRNA vaccines may trigger relapses in AIBD patients. Vaccines are important in AIBDs patients, since the latter are characterized by a vulnerability against infections in the mucocutaneous barrier5: completion of vaccination is advisable, and patients should be treated for flares when needed. However, data on the effect on immunosuppressants on IgG antibodies titres in short and long term are needed. IgG S1-RBD persistence in AIBD patients is also a matter of concern; this should encourage dermatologists to monitor anti-COVID-19 immunity.

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