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Clinical Infection & Immunity

Case Report

Volume 7, Number 2, September 2022, pages 58-61

Stevens-Johnson Syndrome From Heterologous COVID-19 Vaccine: A Case Report

Stevens-Johnson syndrome (SJS) is a rare, acute, and life-threatening mucocutaneous disease that is often drug-induced. It is a result of extensive keratinocyte cell death resulting in significant scalded skin appearance. Other rare causes include infections and immunizations. The average mortality rate of SJS in elderly is 1-5% and those with very large epidermal detachment has 25-35% mortality rates [1]. SJS is essentially diagnosed clinically. Constitutional symptoms such as fever, malaise, pain in swallowing and joint pains were recorded in the patient’s history. Skin manifestations usually present as erythematous purpuric macules which eventually coalesce forming large patches. Most of the time, cases will show oral manifestations described as painful crusts and erosions [2].

In 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused a pandemic. This led to the emergence of coronavirus disease 2019 (COVID-19) vaccines. Due to its novelty, little is known regarding its side effects. Since the start of vaccinations, many dermatological manifestations have been described. McMahon et al defined subset of vaccine-related eruption following COVID-19 vaccination [3]. With the current recommendation of having a third dose, heterologous COVID-19 vaccines have been granted emergency use to accelerate vaccine roll-out worldwide, especially in low- and middle-income countries [4]. However, the safety profile of using heterologous vaccination has not yet been well elucidated.

In this case report, a serious dermatological adverse event after giving booster dose using heterologous vaccination will be discussed.

This patient is a 62-year-old Filipino male, with hypertension, diabetes mellitus, and chronic obstructive pulmonary disease for years, presented with 1-week history of fever and skin lesions. He was apparently well until 1 week after receiving his third dose using mRNA-1273 (mRNA platform, Moderna) COVID-19 vaccine. He experienced multiple erythematous purpuric rashes mostly on the trunk accompanied by fever, pain on swallowing and malaise. He then sought consult with a private physician and was given topical corticosteroids, anti-pyretic and anti-histamines. Only slight relief of symptoms were noted. After 3 days, his skin lesions became more generalized, and his eyes were now affected. He went to the emergency room and subsequent admission was advised.

On physical examination he looked unwell. His vital signs were within normal limits. Cutaneous examination showed generalized brown to hyperpigmented purpuric macules with surrounding erythema with few areas showing bullae, accompanied by tenderness. Mucosal involvement was present in the form of hemorrhagic crusts over the lips, erythema of the buccal mucosa, redness, and discharge from the eyes (Figs. 1, 2). Patient was also complaining of difficulty of swallowing due to pain around the oral mucosa, but no erosions noted.

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Figure 1. Erythematous macules coalescing into erythematous patches over the trunk and face, and hemorrhagic crusting of the eyes.

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Figure 2. Generalized brown to hyperpigmented macules with surrounding erythema with beginning erosion.

The diagnosis of SJS was suspected. Detailed drug history was elicited which revealed that for the past 2 years patient had been taking angiotensin-converting enzyme (ACE) inhibitor for his hypertension, sitagliptin for his diabetes and salmeterol fluticasone puff for his chronic obstructive pulmonary disease. Since taking all these medications, there were no side effects noticed. No other recent medications taken that can contribute to the development of skin rashes. He did not report any allergies to medication and food. He denied smoking and drinking alcoholic beverage drink. His initial two doses of COVID-19 vaccine were completed 6 months ago, using inactivated whole-virus vaccine (Sinovac). During this time, no adverse event was observed. In this case, the diagnosis of SJS from the third dose of COVID-19 vaccine was made based on the timeline, disease course, and morphology of the cutaneous findings described as sudden appearance of generalized erythematous purpuric macules coalesced into sheets of necrosed skin with mucosal lesions and constitutional symptoms.

On admission, he was placed in an isolated room to avoid infection. Laboratory workups were requested which include complete blood cell (CBC) count, blood urea nitrogen (BUN), creatinine, liver enzymes, electrolytes, and glycated hemoglobin (HbA1c) (Table 1). He had elevated creatinine and liver enzymes on admission. Serial monitoring was done during his stay in the hospital. Referral to Dermatology and Ophthalmology were immediately placed. He was started on hydrocortisone 100 mg/intravenous (IV) every 8 h for 5 days and diphenhydramine/IV. Topical skin care was plain petroleum jelly. Application was instructed to be in a sterile environment. Mouthwash composed of mixed 120 mL aluminum hydroxide and magnesium hydroxide, 120 mL diphenhydramine solution, 2% lidocaine solution and 20 mL distilled water was instructed to be gargled three times a day to relieve the pain in the oral mucosa. Ophthalmology immediately treated him with fusidic acid ophthalmic solution and preservative-free hydrating eye drops. Contact precaution was strictly followed.

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Table 1. Laboratory Workups on Admission

After 5 days, his lesions started to regress as well as his constitutional symptoms. Hydrocortisone/IV was discontinued. Complete resolution of skin lesion was noted after 24 days, and his laboratory parameters improved. He was discharged well.

SJS is a rare, severe, and potentially fatal, delayed type IV hypersensitivity reaction. Medications are by far the most common trigger of this condition. In very rare instances, SJS could be caused by vaccination [3]. Incidence is 1.2 - 6.0 per million person-years for SJS, and 0.4 - 1.2 per million person-years for toxic epidermal necrolysis (TEN) [4]. Diagnosis is essentially clinical. It presents with a prodrome usually recorded as sore throat, fever, malaise, and arthralgia preceded by cutaneous manifestations. Morphology of the skin lesions can initially start as erythematous, dusky red or purpuric macules and have tendency to coalesce. Ninety percent of the time, erosions of the buccal, ocular, and genital mucosae are present [5].

In this case report, our patient experienced mucocutaneous manifestations with fever which clinically fits SJS 1 week after initiation of the third dose of COVID-19 vaccine using mRNA-1273. Causality assessment is important in managing SJS and this could be associated to his recent vaccination.

SJS is extremely rare with vaccination. There were few reported cases in the literature and some of the vaccination mentioned to cause SJS were combined measles, mumps, rubella vaccine and influenza vaccine [6]. In influenza vaccine for example, rather than the attenuated viral antigens themselves, adjuvants or preservatives might be responsible for evoking SJS [7]. Additives in vaccine have been known to cause drug eruptions. Thiomersal is a representative additive in vaccine and is used as a preservative in various presentations. It has been reported to be a possible causative agent for vaccine-induced drug eruptions [8].

Lately, there are few reports with COVID-19 vaccines causing SJS/TEN. It has two components (virotopes and excipients), and both can cause severe drug reactions. In the presented case we hypothesized that the virotopes of the vaccines have been believed to cause SJS. The expression of the virotopes “vaccine antigens” on the surface keratinocytes, leads to a CD8⁺ T-lymphocyte response against epidermal cells and causes apoptosis of keratinocytes and detachment of dermo-epidermal junction leading to SJS in genetically susceptible individual [9].

There are multiple COVID-19 vaccines that have been approved for emergency use to accelerate vaccine roll-out. Heterologous prime-booster has been implemented most especially in low to middle income countries. This case adds to the evidence of a possible rare severe dermatological side effect from the vaccine. However, the benefit still outweighs the risk and should not cause hesitancy in receiving vaccination.

Acknowledgments

The authors would like to thank the Department of Internal Medicine of Bataan Peninsula Medical Center for their support in writing this case report.

Financial Disclosure

None to declare.

Conflict of Interest

None to declare.

Informed Consent

The patient in this manuscript gave written informed consent for the publication of his case details.

Author Contributions

Camelia Faye R. Tuazon, MD contributed to clinical evaluation and management of the patient and writing and editing of the manuscript. Cloudine Denise A. Tumulak, MD contributed to clinical evaluation and management of the patient.

Data Availability

The data supporting the findings of this report are available from the corresponding author upon reasonable request. Any inquiries regarding supporting data availability should be directed to the corresponding author.

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Clinical Infection and Immunity is published by Elmer Press Inc.