A case of generalized Sweet syndrome with vasculitis triggered by recent COVID-19 vaccination

Introduction

Sweet syndrome (SS), also known as acute febrile neutrophilic dermatosis, is an uncommon dermatosis characterized by fever, neutrophilia, and multiple erythematous painful plaques. Histologically, it presents with a dense dermal neutrophilic infiltration. SS is often associated with hematologic malignancies, including plasma cell dyscrasias. Herein, we report a rare case of SS with vasculitis and transient IgA monoclonal gammopathy triggered by a Janssen Ad26.COV2.S vaccine.

Case report

A 54-year-old man with no significant past medical history presented to the emergency department in significant pain, with tongue swelling and ulceration. The patient denied fevers, chills, night sweats, and weight loss. He had received the Janssen Ad26.COV2.S vaccine 9 days prior to symptom onset.

On physical examination, he had an erythematous, fissured tongue with confluent erosions (Fig 1, A) and dozens of firm, blanching and erythematous and papulonecrotic nodules on the extremities and trunk (Fig 1, B). The scrotum had flesh-colored and erythematous plaques. The plantar aspects of the feet had erythematous and targetoid macules (Fig 1, C). The patient's lesions progressed over one week, and he developed new eroded and crusted plaques on the scalp, trunk, and extremities. The genital (Fig 1, D) and plantar foot lesions became more targetoid in appearance.

Fig 1.

Physical examination revealed an enlarged, erythematous painful tongue with many papules and fissures with overlying exudate (A); erythematous, firm nodules with slightly eroded centers on the dorsal aspects of the hands and extremities (B); tan, firm verrucous nodules, some with central pinpoint hemorrhage (C), which progressively became more targetoid in appearance (D).

Lab work revealed leukocytosis (10.84 × 10³/uL) with 90% neutrophils, an erythrocyte sedimentation rate of 29 mL/h, and a C-reactive protein concentration of 19.6 mg/L. Serum protein electrophoresis resulted in a positive abnormal monoclonal IgA lambda. Additional rheumatologic, including tests for antineutrophil cytoplasmic antibodies and antinuclear antibody, and infectious workup was otherwise negative. The patient was negative for COVID-19 on nasal polymerase chain reaction, and COVID-19 serologies were negative. Computed tomography of the chest, abdomen, and pelvis were unremarkable.

Three 3-millimiter punch biopsies were performed for direct immunofluorescence, hematoxylin-eosin staining, and tissue cultures for fungi and bacteria, including acid-fast bacilli. Hematoxylin-eosin staining demonstrated a dense interstitial and perivascular neutrophilic infiltrate with leukocytoclasia and focal fibrin deposition in blood vessel walls (Fig 2, A to C). Notably, we did not appreciate papillary dermal edema. The direct immunofluorescence and cultures were unremarkable. The patient was treated with a 10-day course of steroids with significant improvement of the lesions. Furthermore, repeat serum protein electrophoresis perfomed approximately 10 weeks after disease onset showed resolution of monoclonal IgA lambda. Thus, we diagnosed a case of SS with vasculitis and transient monoclonal IgA gammopathy, triggered by the Janssen Ad26.COV2.S vaccine.

Fig 2.

Hematoxylin–eosin–stained sections showing (A, B) a diffuse neutrophilic infiltrate in the interstitial dermis associated with prominent leukocytoclasia and (C) neutrophils surrounding and involving a blood vessel, which also exhibits fibrin deposition. (Original magnifications: A, ×40; B, ×200; C, ×400.)

Discussion

The major diagnostic criteria for SS include the abrupt onset of painful erythematous plaques or nodules and histopathologic evidence of neutrophilic dermal infiltrate without leukocyoclastic vasculitis.¹ The minor criteria for SS include fever; symptoms preceded by upper respiratory or gastrointestinal infections, or associated with vaccinations, malignancy, inflammatory disorders, or pregnancy; abnormal white blood cell count and inflammatory markers; and improvement with systemic steroids. Although the absence of vasculitis has been a historical criterion for the diagnosis of SS, reports have suggested that vasculitis should not exclude this disorder.^2,3

COVID-19 can infect endothelial cells, leading to intravascular inflammation and cutaneous vasculitis, and a recent study reported the appearance of monoclonal bands in the proteinogram of COVID-19 patients.⁴ The data suggest that increased production of interleukin 6 results in differentiation of B-cells and hyperstimulation of the humoral response, resulting in aberrant immunoglobulin production and a transient plasma cell dyscrasia.⁴ Class switching from immunoglobulin M to IgG/IgA typically occurs within 7 to 10 days, which coincides with this patient's onset of symptoms.⁵ In fact, a robust postvaccination class switch from immunoglobulin M to IgA may account for his monoclonal gammopathy at the time of presentation. For our patient, given the transient nature of the monoclonal gammopathy, a consulting hematologist did not recommend further workup of his monoclonal gammopathy with bone marrow biopsy. There have been several reports of cutaneous vasculitis precipitation or exacerbation, including leukocytoclastic vasculitis, urticarial vasculitis, antineutrophil cytoplasmic antibody-associated vasculitis, and Henoch-Schonlein purpura, secondary to the use of current Food and Drug Administration-approved vaccines for SARS-CoV-2.6, 7, 8, 9 Our patient presented with generalized SS with histopathologic evidence of vasculitis 10 days after receiving the Janssen Ad26.COV2.S vaccine. We postulate that an immune response similar to COVID-19 infection was experienced in our recently vaccinated patient. Following treatment, the IgA monoclonal gammopathy resolved, highlighting the transient nature of immunoglobulin response and subsequent vasculitis. It is imperative for physicians to be aware of these significant yet transient side effects and to understand that they are not a contraindication for vaccination against SARS-CoV-2.

Conflicts of interest

None disclosed.