Pyoderma gangrenosum following vaccination against coronavirus disease‐2019: a case report

Dear Editor,

Vaccination reduces the risk of infection and severity of coronavirus disease‐2019 (COVID‐19). However, various skin reactions associated with COVID‐19 vaccination have been reported. ¹ The most common skin adverse reactions are local site reaction, urticaria, morbilliform, and delayed large local reaction, while immune‐mediated dermatoses and herpes virus reactivation are also observed. Here, we report a rare case of pyoderma gangrenosum (PG) following COVID‐19 vaccination.

A 29‐year‐old man was referred to our institution for a 1‐month history of gradually enlarging painful skin ulcers on the right lower extremity. A lesion initially presented with erythema and swelling 2 days after receiving the second dose of tozinameran (BNT162b2, Pfizer‐BioNTech). Local injection site reactions, fever, fatigue, and headache were not observed after the vaccination. Over the course of a month, multiple new‐onset small skin ulcers appeared. Past medical history revealed hyperuricemia and dyslipidemia, which were treated with dotinurad and atorvastatin calcium hydrate, respectively. Physical examination showed multiple well‐demarcated skin ulcers on the right lower extremity (Fig. 1a). Laboratory tests demonstrated elevated C‐reactive protein (0.98 mg/dl [normal, 0.00–0.14 mg/dl]) and IgG (2682 mg/dl [normal, 861–1747 mg/dl]) levels. Complete blood count showed slight thrombocytosis (36.6 × 10⁴/μl [normal, 15.8–34.8 × 10⁴/μl]) with normal white blood cell count. Coagulation studies revealed normal prothrombin time and activated partial thromboplastin time. Liver and renal function tests were unremarkable. Serology demonstrated normal levels of antinuclear antibodies and antineutrophil cytoplasmic antibodies. Histopathological analysis of tissue biopsy from the skin ulcers and peripheral areas revealed central necrotizing suppurative inflammation with ulceration and superficial dermal edema (Fig. 1b). Moreover, dense dermal infiltration of neutrophils, lymphocytes, and plasma cells was observed in the absence of apparent vasculitis and epithelioid cell granulomas (Fig. 1c). Tissue microbial cultures did not detect any bacteria, fungi, or atypical mycobacteria. These findings were consistent with a diagnosis of PG. Treatment with oral prednisolone 30 mg/day (0.3 mg/kg/day) gradually improved his skin lesions.

Figure 1.

(a) Multiple skin ulcers on the right lower extremity. (b) Histopathology, showing central necrotizing suppurative inflammation with ulceration (H&E, ×40). (c) Dense infiltration of neutrophils, lymphocytes, and plasma cells in the dermis (H&E, ×100)

PG is often associated with systemic diseases, such as rheumatoid arthritis, inflammatory bowel disease, and other autoimmune and inflammatory diseases. ² While the exact pathophysiologic mechanisms of PG remain unclear, autoimmune processes driven by abnormalities in the innate immune system are implicated. ² Unlike conventional PG, vaccination‐associated PG presents without associated systemic diseases. ³ In our case, it is highly likely that COVID‐19 vaccination could have contributed to the development of PG due to their close temporal relationship. Among the few cases of PG following COVID‐19 infection, ⁴ , ⁵ it was speculated that COVID‐19 infection may trigger the development of PG because pro‐inflammatory cytokines (IL‐6 and IL‐8) are central in the pathogenesis of both conditions. TNF‐α, IL‐12/23, and IL‐6 are the important cytokine pathways implicated in the pathogenesis of PG. Cutaneous adverse reactions associated with COVID‐19 vaccination can be divided according to the cytokine profiles based on the preponderance of specific T‐cell subsets. ¹ Considering the key cytokines in the pathogenesis of PG, it is speculated that Th1/Th17 polarized cutaneous inflammation was induced by COVID‐19 vaccination, leading to the development of PG in our case.