COVID-19 vaccines approved to date require two partial vaccinations to achieve the highest possible immunity, but the duration of vaccine protection is currently unknown. The occurrence of dermatologic reactions after the first dose of the Pfizer-BioNTech vaccine BNT162b2 (Cominarty®) appears to be rare.¹ However, data on adverse events after the second dose are still limited.

Here, we report a 22-year-old man who presented to our department because of significant worsening of pre-existing vitiligo and symmetrical appearance of new lesions across his face, 2 weeks after the second dose of the vaccine (Figure 1B,D). The patient had received no systemic and topical treatment, which could induce activation of an inflammatory process. The patient had a history of vitiligo on only a localized area on the face which had been treated with topical tacrolimus 0.1% two times a day and a clinical response had been achieved at the end of 6 months.(Figure 1A,C). A physical examination revealed that the patches were clinically consistent with vitiligo, and examination under Wood lamp confirmed the diagnosis. There were no vitiligo macules seen at any other body site. There was no family history of vitiligo. Results of laboratory investigations showed vitamin D level at 28.7 ng/ml (30–80 ng/ml), antinuclear antibodies (ANA) at 1:100 (<1/100), negative thyroid autoimmunity, and a very high level of SARS-CoV-2 IgG at 53837 AU/ml (<50 AU/ml, negative; >50 AU/ml positive). He was treated again with topical tacrolimus twice a day; unfortunately, there was no response during a 2-month follow up.

Large cohort studies have reported the development of autoantibodies after COVID-19 vaccines. mRNA vaccines have been shown to produce a predominant Th1-type response, producing high levels of TNFa, IFNγ, and IL2. This could explain autoimmune diseases flares like vitiligo that have a proven Th1 role in its pathogenesis.²

Patients with vitiligo have an increased concentration of circulating autoantibodies that are specific to melanocyte cytoplasm and surface antigens.³ Circulating antibodies penetrate melanocytes leading to melanocyte destruction, impaired melanogenesis, and melanocyte apoptosis. If antimelanocyte antibodies present in the circulation in patients with vitiligo are blocked by antiviral ones, the destructive effects on melanocytes would be stopped or delayed. Thus, vaccine against COVID-19 may protect against vitiligo. On the other hand, it is possible that COVID-19 antibodies may react synergically with antimelanocyte antibodies resulting in melanocyte impairment and exacerbating of vitiligo areas as seen in our patient who had also low vitamin D levels. Accumulating data have suggested the association of vitamin D with vitiligo etiopathogenesis. Vitamin D ligands suppress cytotoxic T lymphocytes and inhibit several pro-inflammatory cytokines such as TNFa and IFNγ, which are known to play an important role in T cell-trafficking to the skin. Furthermore active vitamin D is known to increase the levels of immunosuppressive cytokine IL-10 and gene polymorphisms of the IL-19 cluster, which belongs to the IL-10 family, have been found to be associated with vitiligo. These findings strengthen vitamin D's protective effects in the vitiligo process.⁴

Presently, there is inadequate data to recommend any COVID-19 vaccine. It has been suggested that checking the antibody titers after vaccination and using the additional vaccinations, if needed, would boost the level of protective antibodies; however; there is no evidence to support it. In our patient, antibody level was found to be very high.

mRNA vaccine should be administered with careful consideration to patients with autoimmune disease. It is not clear if the appearance of vitiligo patches is related to the second dose of vaccination. We suggest that inactivated virus vaccine should be administered as is suggested in patients with MS.⁵