Stevens‐Johnson syndrome induced by Vaxvetria (AZD1222) COVID‐19 vaccine

Conflicts of interest

None of the authors have any conflict of interest to disclose.

Funding sources

The authors declare that no financial or industrial support was provided for this work.

To the editor,

A 65‐year‐old male patient with unremarkable medical history, except for recent administration of the second dose of Vaxvetria (AZD1222) COVID‐19 vaccine, was hospitalized for a mucocutaneous eruption occurred 10 days after the injection. No adverse events were reported after the first dose. A prodromal phase characterized by headache, high fever, cough, impaired vision and joint and muscle pain started 3 days after the vaccine. At dermatological consultation, multiple, round‐to‐oval erythematous patches were observed, with ill‐defined borders and purpuric centres giving the lesions an atypical targetoid appearance. The patches were widely distributed on face, trunk and limbs, sparing the scalp, palms and soles with an approximate body surface area (BSA) involved of 9% (Fig. 1a). Mucosal involvement was also presented with erosions and vesicles affecting both superior and inferior labial mucosae and glans penis (Fig. 1b). A skin biopsy was collected, and the histological report evidenced hyper‐orto‐parakeratosis with focal vacuolar degeneration of the basal layer and scattered apoptotic keratinocytes. Clinical and pathological findings were compatible with Stevens‐Johnson syndrome (SJS), thus prednisone 1 mg/Kg/die was started and slowly tapered in 8 weeks, resulting in progressive improvement and complete clearance of lesions (Fig. 1c).

Figure 1.

Clinical pictures showing cutaneous and mucosal involvement before (a, b) and after administration of corticosteroids (c).

Blood examinations of the prodromal phase showed neutrophilia and low platelets along with elevated CRP (9.21 mg/dL), LDH (319 U/L) and fibrinogen (>700). Subsequently, an increase in CRP (14.73), creatine‐kinase (299 U/L), LDH (345 U/L) and d‐dimer (from 1984 to 2256 μg/mL) were noted with fibrinogen consumption. However, coagulation indexes (PT and aPTT) appeared to be normal, excluding intravascular coagulation disease. A cranial CT angiography was performed due to persistence of headache, revealing superior sagittal sinus thrombosis (Fig. 2) for which the patient was started with Warfarin. A venous echo colour Doppler excluded deep vein thrombosis of lower limbs.

Figure 2.

Radiological images from cranial CT Angiography conducted during hospitalization showing irregular uptake at superior sagittal sinus, compatible with thrombosis.

Stevens‐Johnson syndrome is a rare life‐threatening inflammatory mucocutaneous reaction, counting 1‐2 cases per million each year. It usually begins with upper respiratory tract symptoms followed by the rapid onset of mucocutaneous lesions, characterized by diffuse erythematous macules with purpuric necrotic centres and overlying blistering. If involvement progresses, affected portions of the skin may slough, resulting in extensive superficial detachments. ¹ Among the defined triggers of SJS, drugs are considered the most important. In our case, no new medications were introduced before the eruption onset. As it appeared 7 days after the administration of the second dose of Vaxvetria COVID‐19 vaccine, we deposed for a probable causative association. The Naranjo score obtained was 5 even if an accurate score was not applicable. Vaccination‐related cases have been described in the literature, the majority regarding childhood and varicella vaccination. ² However, only a few cases of SJS after COVID‐19 vaccination have been reported in the literature so far, ³ , ⁴ , ⁵ , ⁶ none of them regarding Vaxvetria vaccine. It has been hypothesized that due to individual genetic susceptibility, vaccine antigens may be preferentially expressed on the surface of keratinocytes, generating a CD8+ T lymphocyte immune response against epidermal cells (type IV hypersensitivity) then leading to apoptosis of keratinocytes and detachment at the dermal‐epidermal junction with a latency of 5 days in most cases ⁷

Intriguingly, our patient presented to the ER with thrombocytopenia and developed sagittal sinus thrombosis during hospitalization. Those manifestations are now known to be possibly linked to an autoimmune dysregulation induced by COVID‐19 vaccination, presumably involving the production of antibodies against platelet factor 4, causing platelet consumption and thrombus formation. ⁸ Therefore, although not demonstrated, we may have observed antibody and cell‐mediated hypersensitivity, induced by COVID‐19 vaccination in the same patient in a short period of time.

During the current COVID‐19 pandemic, vaccination is the safest available option to stop the pandemic and prevent severe disease. Given the large number of persons likely to be exposed to these drugs, vaccine safety is a critical issue: identifying and managing adverse reactions, while continuing to educate on the critical importance of vaccination is an objective of primary importance.

Informed consent

The patients have given written informed consent to the publication of the case details.

Data availability statement

Data sharing is not applicable to this article as no datasets were generated or analysed during the current study.