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Pyoderma Gangrenosum after COVID-19 Infection and Vaccination

      Keywords

      To the Editor:

      Introduction

      Pyoderma gangrenosum (PG) is a rare, autoinflammatory neutrophilic dermatosis that is characterized by highly painful purulent pustules or deep, enlarging ulcers with purple and undermined edges.1 PG has been associated with systemic diseases including HIV, hepatitis, systemic lupus erythematosus, ulcerative colitis, inflammatory bowel disease, and Takayasu arteritis;1 however, there remains limited discussion on occurrences of PG after COVID-19 infection and vaccination despite multiple documented cases. We present a review of PG onset after COVID-19 infection and vaccination and its implications for both adverse effects monitoring and patient counseling.

      Methods

      Literature searches were conducted on PubMed and Google Scholar ranging from 2019 to July 2022. Ten contributions were selected based on subject relevance; novel PG onset, and PG flares after COVID-19 infection and vaccination were included. Citations within the selected papers were also screened for relevance.

      Results

      To date (7/2022), there have been four cases of PG after COVID-19 vaccination and six cases of PG after COVID-19 infection (Table 1, Appendix).
      Table 1Reported Cases of Pyoderma Gangrenosum after COVID-19 Infection and Vaccination
      Patient ProfileAfter Infection or Vaccination?COVID-19 Vaccine TypeOnset (days after vaccine administration/infection)Location of LesionsTreatmentClinical Outcome
      29-year-old male 2

      VaccinationTozinameran, 2nd dose2 daysRight lower legOral prednisolone 30 mg/day (0.3 mg/kg/day)Gradual improvement with therapy
      73-year-old female 3

      VaccinationTozinameran, 2nd dose14 days

      (flare)
      Left pretibial regionInfliximab injection, oral prednisone, cyclosporine, biweekly adalimumab injectionsInjection reaction to infliximab, unresponsive to all other treatments
      49-year-old male 7

      VaccinationTozinameran, 2nd dose22 daysUpper arm injection site (unspecified laterality)Topical and systemic corticosteroids (prednisone 1 mg/kg/day)Resolution after 1 month of therapy
      27-year-old male 8

      VaccinationTozinameran, 1st dose1 dayRight lower leg and upper posterior thigh, left lower leg, perianal region, dorsal right handIntravenous prednisone 1 mg/kg/dayRapid improvement in 3 days, complete resolution in 21 days
      66-year-old male 6

      InfectionNot applicable (N/A)33 daysSacral regionNegative-pressure wound therapy (NPWT) x 1 month, pedicled superior gluteal artery perforator flap for wound closureNo post-operative complications, discharged 33 days after surgery
      52-year-old male 6

      InfectionN/A42 daysSacral regionNPWT x 6 weeks, pedicled superior gluteal artery perforator flap for wound closure

      No post-operative complications
      71-year-old male 4

      InfectionN/A10 daysPenis, left scrotum, groin, buttocks, and abdomenPrednisone 60 mg daily, topical corticosteroids, and infliximab for long-term treatmentPrompt improvement with steroid therapy
      44-year-old female 9

      InfectionN/A∼90 days (after bilateral mastectomy)Nipple areolar complex of both breastsSteroids, then infliximabClinical improvement on steroids, wound dehiscence after discharge. Steady improvement on infliximab.
      72-year-old male 10

      InfectionN/AUnspecifiedLeft scrotumPrednisone prior to loose wound edge approximation. Cyclosporine and infliximab for post-procedural therapy.Improved on prednisone, scrotal prolapse requiring loose wound edge approximation. Complete wound healing at 5-months
      41-year-old male 5

      InfectionN/AUnspecified; 8 days prior to hospital admission

      (flare)
      Upper back, left trunk, right armIntravenous methylprednisolone, topical clobetasol dipropionate 0.05%Unresponsive to in-hospital therapy, referred to the burn center.

      Discussion

      Multiple authors have hypothesized that exposure to the COVID-19 spike protein antigen via infection or vaccination may trigger an autoimmune response that mediates PG.2–5 This is due to the pathogenesis of COVID-19 and PG both involving the activation of proinflammatory cytokines including interleukin-6 (IL-6), IL-8, IL-12, IL-23, and tumor necrosis factor-ɑ (TNF-ɑ).2,3,5 Both are also associated with elevated neutrophils and dysregulation of the Janus Kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway.3,4 Finally, it is hypothesized that COVID-19 vaccination can trigger cutaneous inflammation from the polarization of T-helper 1 cells (Th1) and Th17 cells to induce PG.2
      The associations between COVID-19 and PG in some of these patients have been challenged by independent risk factors including pressure ulcers from long-term ICU hospitalization,6 a history of ulcerative colitis (UC),7 injection of subcutaneous granulocyte colony-stimulating factor (G-CSF),7 and cocaine use.5 Risk factors such as UC and G-CSF treatment may predispose patients to PG-inducing autoimmune reactions triggered by COVID-19 infection/vaccination.7 The patients who developed pressure ulcers and subsequent PG in the ICU were initially hospitalized for severe COVID-19, indicating how COVID-19 infection may mediate conditions that favor PG development.6

      Conclusions

      PG is an exceedingly rare complication following COVID-19 infection and vaccination. Given that only 47 incidences of PG have been reported to VigiBase (the World Health Organization's global database for suspected adverse effects) after the administration of over 12.2 billion COVID-19 vaccine doses as of 7/15/2022, the benefits of COVID-19 vaccines still significantly outweigh the risks. We advise healthcare providers to continue advocating for the importance of obtaining the COVID-19 vaccine while monitoring for rare but severe adverse effects such as PG in patients with a history of COVID-19 infection and vaccination.

      Funding sources

      The authors declare no source of funding.

      References

      • 1. Miller J, Yentzer BA, Clark A, Jorizzo JL, Feldman SR. Pyoderma gangrenosum: A review and update on new therapies. J Am Acad Dermatol. 2010;62:646-654.
      • 2. Toyama Y, Kamiya K, Maekawa T, Komine M, Ohtsuki M. Pyoderma gangrenosum following vaccination against coronavirus disease‐2019: a case report. Int J Dermatol. 2022;61:905-906.
      • 3. Clark AL, Williams B. Recurrence of Pyoderma Gangrenosum Potentially Triggered by COVID-19 Vaccination. Cureus. Published online February 26, 2022. doi:10.7759/cureus.22625
      • 4. Syed K, Chaudhary H, Balu B. Pyoderma gangrenosum following COVID-19 infection. J Community Hosp Intern Med Perspect. 2021;11:601-603.
      • 5. Adams J, Habenicht D, Gibran Y. COVID-19 infection and treatment-resistant cocaine-induced pyoderma gangrenosum: A case report. Ann Med Surg. 2022;78:103828.
      • 6. Elkhatib R, Giunta G, Hanssens V, et al. Case Report of Two Patients With COVID-19 and Sacral Pressure Injuries Associated with Pyoderma Gangrenosum. Adv Skin Wound Care. 2021;Publish Ahead of Print. doi:10.1097/01.ASW.0000744356.54317.c2
      • 7. Franceschi J, Darrigade AS, Sanchez‐Pena P, Legrain‐Lifermann V, Milpied B. Pyoderma gangrenosum after mRNA-based SARS-CoV-2 vaccine. J Eur Acad Dermatol Venereol. Published online July 11, 2022:jdv.18389. doi:10.1111/jdv.18389
      • 8. Barry M, AlRajhi A, Aljerian K. Pyoderma Gangrenosum Induced by BNT162b2 COVID-19 Vaccine in a Healthy Adult. Vaccines. 2022;10:87.
      • 9. Rich MD, Sorenson TJ, Schubert W. Post‐surgical pyoderma gangrenosum in otherwise healthy patient with history of COVID‐19. Breast J. 2021;27:671-674.
      • 10. Hasan M, Kim Y, Clark JY. Loose scrotal wound edge approximation in the setting of pyoderma gangrenosum after COVID-19 infection. Urol Case Rep. 2022;42:102017.

      Conflicts of Interest

      The authors have no conflicts of interest to declare.

      Acknowledgements

      None

      Appendix

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