The histologic and molecular correlates of COVID-19 vaccine-induced changes in the skin

Abstract

Twenty two patients who had developed an adverse cutaneous reaction to the Moderna or Pfizer vaccine underwent biopsies. Each case was assessed light microscopically and in select biopsies spike glycoprotein and cytokine assessment were also conducted. The patients developed self-limited cutaneous reactions often described clinically as urticarial or eczematous within one day to 4 weeks after receiving the first or second dose of the Pfizer or Moderna vaccine. Classic clinical and morphologic depictions of type IV cutaneous hypersensitivity with features of dermatitis, interface dermatitis, granulomatous inflammation and/or lymphocytic vasculitic component were observed. Clinical and/or histologic features of perniosis, pityriasis rosea, pityriasis rubra pilaris and guttate psoriasis were seen in select cases. In two cases the dominant picture was urticarial vasculitis, possibly reflective of an Arthus type III immune complex action. The biopsies of normal skin post-vaccine and skin affected by the post vaccine eruption showed rare deep microvessels positive for spike glycoprotein without complement deposition contrasting with greater vascular deposition of spike protein and complement in skin biopsies from severe COVID-19 patients. It is concluded that self-limited hypersensitivity reactions to the vaccine occur possibly due to a substance found in the vaccine vehicle such as polyethylene glycol. An immune response that is directed against human-manufactured spike has to be considered since some of the reactions clinically and or histologically closely resemble mild COVID-19. Finally, vaccine associated immune enhancement largely attributable to the adjuvant properties of the vaccine may unmask certain inflammatory milieus operational in psoriasis, atopic dermatitis and subclinical hypersensitivity.

A case of erythroderma with elevated serum immunoglobulin E and thymus and activation‐regulated chemokine levels following coronavirus disease 2019 vaccination

“…There is a possibility that the patient's cutaneous symptoms may be fully due to COVID-19 vaccination, while there is another possibility that the first symptoms that were caused by COVID-19 vaccination may have been worsened and prolonged by repetitive scratching. Magro et al described the histopathological findings of COVID-19-vaccine-induced changes in the skin 3. They reported that the most common pattern was eczematous dermatitis and/or concomitant cytotoxic interface dermatitis, which was also observed in our case.…”

Pyoderma Gangrenosum Induced by BNT162b2 COVID-19 Vaccine in a Healthy Adult

“…Magro et al studied the biopsies of 22 patients who developed adverse skin changes after receiving mRNA-1273 or BNT162b2 vaccines [3]. They reported interface dermatitis, eczematous dermatitis, lymphocytic vasculitis, Grover's disease, urticarial vasculitis, urticaria, perniosis, and granulomatous inflammation, with one case exhibiting an interstitial pattern and another exhibiting a folliculocentric neutrophilic and granulomatous reminiscent of vesiculopustular pyoderma gangrenosum [3]. Most of the cases reported in the same study demonstrated type IV hypersensitivity reaction and less commonly that of immune-complex-mediated hypersensitivity [3].…”

“…They reported interface dermatitis, eczematous dermatitis, lymphocytic vasculitis, Grover's disease, urticarial vasculitis, urticaria, perniosis, and granulomatous inflammation, with one case exhibiting an interstitial pattern and another exhibiting a folliculocentric neutrophilic and granulomatous reminiscent of vesiculopustular pyoderma gangrenosum [3]. Most of the cases reported in the same study demonstrated type IV hypersensitivity reaction and less commonly that of immune-complex-mediated hypersensitivity [3]. Moreover, Ramessur et al reported a 73-year-old man who developed cutaneous thrombosis associated with skin necrosis following the first dose of the vector-based ChAdOx1 nCov-19 vaccine [6].…”

“…However, as with other vaccines, COVID-19 vaccines can cause a variety of adverse events, including pain or redness at the site of injection, fever, itching, chills, headache, muscle ache, fatigue, and joint pain [2]. Similarly, several cases of COVID-19 vaccine-induced skin changes have been reported, including urticaria, eczematous dermatitis, and granulomatous inflammation [3]. Pyoderma gangrenosum (PG) is a rare inflammatory skin disease characterized by painful pustules or nodules that ulcerate; it is thought to be immune induced by the improper function of neutrophils, leading to neutrophilic dermatosis and causing rapid development of painful cutaneous necrotic ulcerations [4].…”

Post-COVID-19 vaccination shoulder abscess and pleuroparenchymal pulmonary lesion due to Burkholderia pseudomallei

“…Cases of post-vaccination injection abscesses have been reported due to Staphylococcus aureus and Mycobacterial species following the use of Infanrix-Hexa ® (Diphtheria, Tetanus, Pertussis, Polio, Hib, Hep B) and Bacillus Calmette–Guérin vaccines [2] , [3] . COVID-19 vaccine has been reported to induce pyoderma gangrenosum, cellulitis, myositis, and subacromial-subdeltoid bursitis probably due to a complex interplay of neutrophilic activation and subsequent infiltration triggered by the viral antigens as well as type IV or immune-complex-mediated hypersensitivity reactions [4] , [5] . Hence, subtle alterations in immune responses following the vaccination leading to re-activation of B. pseudomallei infection in our patient is a likely possibility.…”