Overlapping acute generalized exanthematous pustulosis drug reaction with eosinophilia and systemic symptoms induced by a second dose of the Moderna COVID-19 vaccine.

Dear Editor,

Lospinoso et al. described a patient with overlapping acute generalized exanthematous pustulosis (AGEP) drug reaction with eosinophilia and systemic symptoms (DRESS) from the Janssen COVID‐19 vaccine (Johnson & Johnson). More recently, O'Connor et al. presented a case of DRESS following the administration of the AstraZeneca COVID‐19 vaccine. Here, we report the case of a middle‐aged Japanese man who experienced a severe cutaneous adverse reaction following the administration of the second dose of the Moderna COVID‐19 vaccine. The differential diagnoses included AGEP, DRESS, and AGEP‐DRESS overlap.

A 43‐year‐old Japanese man presented with fever and erythroderma after receiving a commercially available COVID‐19 mRNA vaccine (Spikevax, Moderna). He received the first dose uneventfully. Within a few hours of the second dose, subjective fever, fatigue, myalgia, and a mildly pruritic eruption developed beginning on the face and intertriginous zones. He complained of chills, sore throat, and hoarseness. He was not taking any medications and had no history of drug allergies either before or after the first dose of the COVID‐19 vaccine. Physical examination revealed variously sized erythematous and edematous pruritic papules and plaques with numerous pinpoint pustules on the face, trunk, intertriginous regions, and extremities with minimal mucous membrane involvement (Figure 1a–c). Histopathological examination showed intraepidermal pustules, spongiosis, papillary edema, and perivascular neutrophilic infiltrate with moderate presence of eosinophils in the upper dermis (Figure 1d,e). Blood examination revealed elevations of eosinophil count, AST (58 U/L), ALT (168 U/L), γGTP (232 U/L), and CRP (4.07 mg/dL). On computed tomography, lymphadenopathy was observed in the bilateral cervical, axillary, and inguinal lymph nodes. Chest computed tomography showed pulmonary emphysema and atelectasis. Endoscopic examination revealed punched‐out ulcers in the esophageal, gastric, and duodenal walls. The patient was administered oral prednisolone at a dose of 1 mg/kg/day (Figure 1f). His skin rash, fever, and laboratory test values improved gradually over the subsequent 5 weeks. In addition, an increase in cytomegalovirus IgG titer (227 AU/mL) was observed on the 35th hospital day, which remained high (365 AU/mL) until the 63rd hospital day, indicating possible reactivation.

FIGURE 1

(a) Face. (b) Right axilla at admission. (c) Chest at admission. (d, e) Histopathological examination (hematoxylin–eosin staining; original magnification, ×40 and ×400). (f) Clinical course after admission. CRP, C‐related protein; γGTP, γ‐glutamyl transpeptidase; PSL, prednisolone.

We described a patient suspected of having AGEP but with features of DRESS occurring as a result of administration of the second dose of the Moderna COVID‐19 vaccine. Of the various conditions classified as severe cutaneous drug reactions, this case exhibited many features that suggested AGEP, such as the timing of the rash and fever with skin lesions beginning on the face and intertriginous zones before disseminating over a few hours. In addition, histopathology showed spongiform subcorneal pustules and perivascular infiltrates with neutrophils and eosinophils. On the other hand, DRESS could not be definitively excluded. Absolute eosinophilia, high fever, organ dysfunction such as liver involvement, and lymphadenopathy are compatible with DRESS, but can also be seen in AGEP. Therefore, we considered that the clinical and histologic morphologies of DRESS and AGEP overlapped in the present case. It is important for clinicians to be aware of this complication in COVID‐19‐vaccinated patients, as this will facilitate a prompt diagnosis and appropriate treatment.

CONFLICT OF INTEREST

None declared.