SARS-COV2 Vaccination and Hidradenitis Suppurativa: Role of Vaccination in Disease Activity

Abstract

Hidradenitis suppurativa (HS) is a severe chronic debilitating inflammatory skin disease of the hair follicle unit that usually presents with painful abscesses, nodules, tunnels and scars in intertriginous areas [1, 2]. Several factors including heat, physical activity, sweating, shaving, premenstrual phase and friction are key players of HS exacerabations [3]. Environmental factors, such as infections and vaccinations, stimulating the immune system could act as a trigger for disease flare. In recent years, a global vaccine campaign against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was launched, and the role of anti-SARS-Cov2 vaccination as trigger for HS flares has been extensively debated [3-5].

We conducted a retrospective study that evaluated the incidence and the characteristics of disease flares in patients with HS who received anti-SARS-CoV-2 vaccination. Data were collected between April 2020 and December 2022 by teledermatology interview, initially preferred due to social distance, or by face-to-face visits when possible. A total of 222 patients, which received at least one dose of COVID-19 vaccine were examined. one hundred and fifty-three patients (68.9%) were vaccinated with BNT162b2 vaccine, 43 (19.4%) with mRNA-1273 vaccine, 16 (7.2%) with ChAdOx1nCoV-19 vaccine, 5 with Ad26.COV2.S vaccine, 4 (1.8%) received the BNT162b2- ChAdOx1nCoV-19 combination, and one patient (0.5%) received the mRNA-1273- BNT162b2 combination (Table 1). Flare was defined as exacerbation of HS occurring within 2 weeks after the onset of SARS-CoV-2 vaccination. Flares after anti-SARS-CoV-2 vaccine were observed in 21 (9.5%) patients, with a mean latency onset of 8.9 days. HS flares positively correlated with a higher Hurley stage at univariate analysis (p  = 0.021). Acute flares were reported among 2.3% (1/42) of patients with Hurley Stage I, 9.1% (14/154) of patients with Hurley Stage II, and 23.1% (6/26) of patients with Hurley Stage III. No association with type of vaccination was observed. No correlation with the concomitant treatment for HS was detected, except for biologic treatment that was associated with a lower risk of flare (non-flares vs. flare: 43.8% vs. 4.8%, respectively; p = 0.034). Although not statistically significant, a positive correlation between female sex and flares was observed (non-flares vs. flares: 88.2% vs. 11.8%, respectively; p = 0.08) (Table 2).

The role of vaccination in HS exacerbations is still discussed. Few case reports described the exacerbation of HS after SARS-CoV-2 vaccination, considering the efficacy and safety of SARS-CoV-2 vaccine in patients with immune-mediated inflammatory diseases [6-8]. Recently, Liakou et al. evaluated the occurrence of flares and new related lesions of HS following SARS-Cov2 vaccination in a retrospective study including 250 HS patients. HS flares occurred in 48 patients (19.2%) following vaccination, while in 9 of them this was the first episode of HS-related lesions. Interestingly, the authors evidenced that the mRNA vaccines were associated with a higher risk of HS flare compared to the non-mRNA vaccines (25.4% vs. 6.2%; p < 0.001). Specifically, the BioNTech/Pfizer vaccine was associated with a higher risk of flare than the Johnson & Johnson vaccine or the AstraZeneca vaccine. Similarly, Moderna vaccine was associated with more flares than the Johnson & Johnson vaccine or the AstraZeneca vaccine. Patients who received mRNA vaccines were 3.5 times as likely to develop HS flare following vaccination compared to those who received non-mRNA vaccines. Moreover, biologic treatment was associated with a lower risk of flare, indicating that biologic treatments may have a protective role against HS flares, possibly due to the downregulation of the immune response to the vaccine [5].

Conversely, our study seems to suggest that the anti-SARS-Cov2 vaccine may not significantly increase the risk of flare in patients with HS. Other retrospective studies confirmed this observation. Pakhchanian et al. conducted a large-scale multicenter retrospective study in which the safety and efficacy of anti-SARS-Cov2 vaccine among HS patients were examined. Out of a total of 1.279.188 vaccinated patients, those with HS were 3418 and had received any dose between BNT162b2 (83%), mRNA-1273 (14.5%) and Ad26.COV.2.S (2.5%). No significant differences emerged between vaccinated and unvaccinated HS patients, also considering patients under long-term HS therapy [9].

This evidence was consistent also in other autoimmune diseases. In a single-center study by Geinsen et al. the activity of chronic inflammatory diseases was assessed before and after each dose of vaccine and was found to be unaffected by vaccination [6]. In addition, Wack et al. in their study analyzed the safety and efficacy of anti-SARS-Cov2 vaccination in patients with immune-mediated diseases and found no additional side effects compared with the healthy population [7]. Yan Xie et al. conducted a meta-analysis of 22 studies to evaluate the relationship between flares and anti-SARS-CoV-2 vaccination in patients with rheumatic disease. Although episode of flares after vaccination were reported, the association was not statistically significant. Therefore, vaccination was recommended in patients with disease in a stable phase [10].

In conclusion, our analysis confirmed the safety in terms of flare of anti-SARS-Cov2 vaccine in patients with HS. Collaterally, biologic agents may act reducing the risk of flare, confirming the observation by Liakou et al. [5]. However, our results do not suggest an association between mRNA vaccines and acute flare and no statistically significant differences were found between the different types of vaccine. Clarifying whether the vaccine can be a trigger of HS acute flare seems to be crucial, to establish the safety of vaccination in HS population and, as recommended in other immune-mediated disease, propose appropriate vaccination campaigns for other infections and so forth seasonal influenza that could potentially represent a trigger disease activity in HS. The main limitations of this study include its retrospective design and the lack of a control group of unvaccinated patients.

Conceptualization: E.M., A.O., and O.S. Data curation: E.D.S. and S.B. Formal analysis: E.D.S. and D.G.; Methodology: M.L.D., G.R., A.M., and G.R. Software: A.M., G.R., and S.B. Supervision: A.O. and O.S. Validation: E.M., A.O., and O.S. Writing–original draft: E.M., E.D.S., and M.L.D. Writing–review and editing: E.M., E.D.S., M.L.D., D.G., A.M., and G.R. All authors have read and agreed to the published version of the manuscript.

The research was conducted in accordance with the principles stated in the Declaration of Helsinki and with the principles of good clinical practice. The study was deemed low risk by the Ethics Committee, thus waiving the need for exempt from ethical approval by the Institutional Review Board (IRB) discussion and approval.

The patients in this manuscript have given written informed consent to the publication of their case details.

The authors declare no conflicts of interest.