Sweet syndrome after the first dose of SARS‐CoV‐2 vaccine (Pfizer‐BioNTech)

Dear Editor,

Since the approval of the emergency use authorization in December 2020, more than half of the world's population has received SARS‐CoV‐2 vaccines. Before authorization, clinical trials had reported the short‐term safety and adverse events after administration of the primary series. ¹ However, real‐world data revealed unexpected various cutaneous manifestations. ² Here, we report a case of severe Sweet syndrome (SS) following BNT162b2 (Pfizer‐BioNTech) vaccination.

A 60‐year‐old man presented with a two‐week history of sudden painful erythematous nodular eruption on the face, trunk, and limbs, which occurred within 2 weeks of the first SARS‐CoV‐2 vaccination. The patient had mild cytopenia with a leukocyte count ranging from 1.54 to 2.91 × 10³/μl for 10 years and had been taking complete blood counts annually without bone marrow biopsy. He was on metformin, sitagliptin, and gliclazide and denied a history of new medications. Physical examination showed multiple indurated nodules with central ulcers and hemorrhages, especially on his face and distal forearms (Figure 1A–D). Blood tests showed a leukocyte count of 3.57 × 10³/μl with 80.1% neutrophils, platelet count of 44 × 10³/μl, elevated C‐reactive protein (CRP) level of 12.56 mg/dl, and high erythrocyte sedimentation rate (ESR) of 27 mm/h. For further evaluation, the patient was hospitalized.

FIGURE 1.

Physical examination showing multiple indurated ulcerative nodules on the (A) face, (B) chest, (C) upper extremities, and (D) back. Histopathologic analysis of an incisional skin biopsy sample showing (E) inflamed granulation tissue with epithelial hyperplasia and papillary dermal edema (hematoxylin and eosin staining, original magnification x 40), and (F) prominent neutrophilic infiltration with multinucleated giant cell in the dermis (original magnification x 400).

Histopathologic examination revealed marked papillary dermal edema, multinucleated giant cells, and prominent neutrophilic infiltration along with reactive squamous epithelial hyperplasia (Figure 1E, F). No evidence of infection with bacteria, fungi, and mycobacteria was demonstrated on histological staining and repeated tissue cultures. Bone marrow biopsy showed multi‐lineage dysplasia suggestive of myelodysplastic syndrome (MDS). Imaging and autoantibody tests excluded other systemic malignancies and rheumatic diseases. Based on these findings, a diagnosis of SS was made. Because he had uncontrolled diabetes requiring insulin injections, high‐dose corticosteroid monotherapy was contraindicated. Instead, cyclosporine (200 mg/day) and prednisolone (20 mg/day) were started, which dampened acute inflammation of the skin condition. After 1‐week treatment, he was discharged and was maintained on systemic therapy for 1 month until the lesions improved with scarring. CRP and ESR normalized, and mild cytopenia persisted. To date, he has not received the second dose of SARS‐CoV‐2 vaccine and no recurrence occurred until 10‐month follow‐up. MDS did not progress without additional treatment.

SS, also known as acute febrile neutrophilic dermatosis, is a rare cutaneous disease. While the exact etiology remains unknown, it is often associated with infections, drugs, or hematologic malignancies. According to the modified diagnostic criteria by von den Driesch, ³ our patient satisfied two major and three minor criteria. Although fever is the most common systemic manifestation, retrospective studies showed that not all the patients had the clinical features that coined the name of the disease. ³ , ⁴

Development of SS induced by preceding vaccination was described in the literature. ⁵ Although the mechanism is not elucidated, the immunologic responses triggered by the vaccination are thought to evoke the release of G‐CSF and other cytokines, responsible for SS. ⁶ Recent articles have discussed the association between SS and SARS‐CoV‐2 vaccines. ⁶ , ⁷ , ⁸ Unlike the prior studies, this report described a predisposed subject to SS in terms of hematologic malignancy, which may have influenced more severe progression. And long‐term leukopenia and compromised immune responses owing to MDS, in our case, may have led to inadequate cytokine production, resulting in a later onset than in the previous cases. ⁹

Even after 2 years have passed, SARS‐CoV‐2 has not been eradicated. And it is unclear how many booster shots may be needed. This study highlights the importance of considering the possibility of rare vaccination‐induced cutaneous reactions. Careful planning of the subsequent doses and continuous monitoring of adverse events are crucial for the safety and effectiveness of SARS‐CoV‐2 vaccines.

CONFLICTS OF INTEREST

The authors have no conflict of interest to report.

DATA AVAILABILITY STATEMENT

The data that support the findings of this study are available from the corresponding author upon reasonable request.