Reply to ‘Development of severe pemphigus vulgaris following SARS‐CoV‐2 vaccination with BNT162b2’ by Solimani et al

Dear Editor,

We have read with great interest the article recently published by Solimani et al. ¹ who have reported the case of a patient, who developed severe de novo pemphigus vulgaris (PV) following COVID‐19 vaccination with the mRNA vaccine BNT162b2 (Comirnaty®, Biontech/Pfizer). The authors describe that cytokine‐like interleukin (IL)‐4, IL‐17 and IL‐21 produced by COVID‐19 vaccination may be linked to germinal center activation being implicated in autoimmune disorders like PV, especially in its initial phase. In this context, at the Dermatology Centre of the University of Naples Federico II, we collected data on 32 patients with PV who performed three COVID‐19 vaccine doses (mRNABNT162b2 and mRNA‐1273 were the vaccines administered).

In 25 (78.1%) cases, no disease worsening or onset of new lesions was observed. In the remaining 7 (21.9%) cases, the patients experienced disease worsening 5–11 days after the vaccination. Notably, all patients were previously treated with oral corticosteroids±azathioprine, and they were all under control before undergoing vaccination. Table 1 shows patient data with the type of vaccine received, the day of onset of worsening of manifestations, and the baseline treatment the patient was receiving. Fortunately, PV worsening was usually easily managed with increased oral corticosteroid administration. A correlation between disease worsening and the type of COVID‐19 vaccine received was not observed. We agree with Solimani et al. who correlate vaccination that potentiated the T/B cell response, which in turn led to the unwanted onset of PV. There are no data to prove this yet, but it is very likely that cytokines such as IL‐4, IL‐17 and IL‐21 may be produced after vaccine inoculation and play an important role in the onset of autoimmune disorders such as PV. ² , ³

Table 1.

Pemphigus vulgaris flares after COVID‐19 vaccine

	Sex	Age	Vaccine/dose	Days from vaccine/dose	Therapy before vaccination
1	M	69	mRNABNT162b2/3	5 days after first dose	Oral prednisone 1 mg/kg/die
2	M	64	mRNABNT162b2/3	7 days after second dose	Azathioprine 100 mg/die
3	M	71	mRNABNT162b2/3	5 days after second dose	Azathioprine 100 mg/die
4	F	61	mRNA‐1273/3	6 days after first dose	Azathioprine 100 mg/die
5	M	68	mRNABNT162b2/3	8 days after second dose	Azathioprine 50 mg/die
6	F	62	mRNA‐1273/3	11 days after first dose	Azathioprine 100 mg/die
7	F	55	mRNABNT162b2/3	7 days after first dose	Azathioprine 50 mg/die

However, cases of exacerbation of PV following other vaccinations such as influenza and tetanus have already been reported in the literature ⁴ , ⁵ ; therefore, we could also hypothesize as in our cases either a hyperimmune reaction induced in genetically predisposed subjects or a cross‐reaction of vaccine antigens with those of pemphigus. This hypothesis could relate the worsening of PV manifestations to the COVID‐19 vaccination. In conclusion, the temporal relationship between COVID‐19 vaccination and PV worsening found in almost 20% of our PV patients underline the possible consequences on PV natural course of COVID‐19 vaccination.

However, fortunately, most patients (80%) usually show no impact on disease, and those who had new manifestations or worsening of the disease were managed without significant complications. All this reinforces the importance and safety of the COVID‐19 vaccine campaign especially in fragile patients such as those with PV where, often, the diagnosis and therapeutic management are not always easy. ⁶ , ⁷ Further studies are needed to deepen the impact of COVID‐19 vaccination on PV course and in PV treatment algorithm.

Conflicts of interest

None to declare for all authors.

Funding sources

None.

Informed consent

Patients gave the consent for photo acquisition and publication.

Data availability statement

Data sharing not applicable to this article as no datasets were generated or analyzed during the current study.