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Coronavirus-disease-2019-associated Stevens–Johnsons syndrome in a 15-year-old boy: a case report and review of the literature
Journal of Medical Case Reports volume 18, Article number: 493 (2024)
Abstract
Background
Stevens–Johnson syndrome (SJS) is a life-threatening condition characterized by high fever and severe mucocutaneous lesions, often triggered by drugs or infection. During the coronavirus disease 2019 pandemic, there was a marked increase in Stevens–Johnson syndrome cases, but relatively few cases were reported in children. The present article reports a pediatric case of Stevens–Johnson syndrome due to coronavirus disease 2019 infection and provides a review of the most relevant literature.
Case presentation
A previously healthy 15-year-old Han Chinese boy from China presented to the hospital with oral ulcers, conjunctival hyperemia, and widespread maculopapular rash. He had a history of fever 9 days prior and tested positive for coronavirus disease 2019 infection. Upon admission, his rash and mucosal lesions worsened, with the development of blisters on the fingertips of both hands, ocular pain, photophobia, and erosive lesions on the genital mucosa with exudation. He was diagnosed with Stevens–Johnson syndrome and received treatment with methylprednisolone, intravenous immunoglobulin, and dermatological and mucosal care. The patient’s condition was managed, and the dosage of high-dose intravenous methylprednisolone was tapered down, followed by a transition to oral prednisolone. He was discharged without sequelae.
Conclusion
We should be aware that coronavirus disease 2019 infection is associated with the development of Stevens–Johnson syndrome in children and may lead to a wide spectrum of dermatologic presentations. Although Stevens–Johnson syndrome is a relatively rare condition, given its potentially serious consequences, it is crucial to identify it as early as possible and to take appropriate preventive and therapeutic measures to reduce complications and improve the quality of life for patients.
Introduction
Stevens–Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is a severe cutaneous mucosal hypersensitivity reaction characterized by the detachment of the epidermis and mucous membrane [1, 2]. It is usually triggered by medications such as anticonvulsants, antibiotics, antiretroviral drugs, and nonsteroidal anti-inflammatory drugs (NSAIDs), and can also be caused by bacterial or viral infections [1, 2]. The SJS-TEN spectrum is categorized on the basis of the percentage of body surface area (BSA) affected by blistered or detachable skin at the peak of the disease. SJS is diagnosed when less than 10% of the BSA is involved, TEN is identified when over 30% is affected, and SJS-TEN overlap is recognized when the affected BSA ranges between 10% and 30% [3].
Coronavirus disease 2019 (COVID-19) is a highly contagious and infectious disease caused by a novel coronavirus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) [4]. It can affect multiple organ systems including, but not limited to, the respiratory, cardiovascular, neurological, gastrointestinal, and musculoskeletal systems. Although the incidence and severity of COVID-19 appeared to be higher in adults during the early stages of the pandemic, it is now recognized as a cause of severe disease in children as well, presenting with a variety of clinical signs and different organ involvement [5]. Skin involvement is common in COVID-19 patients, including urticaria, purpura, and vasculitis. There have been multiple studies of SJS in adults after COVID-19 infection, but only a few cases have been reported in children [6]. Herein, we reported one pediatric case diagnosed with SJS related to COVID-19 infection and provide a review of the most relevant literature.
Case presentation
A previously healthy 15-year-old Han Chinese boy from China developed a fever 9 days prior to admission and was diagnosed with COVID-19 infection. He was initially treated with amoxicillin for 3 days, and his fever had resolved 5 days before admission. However, he developed oral ulcers, conjunctival hyperemia, and a widespread maculopapular rash 4 days prior to admission to our hospital. He and his family have no history of drug allergies or inherited diseases. Upon admission, his vital signs were as follows: body temperature 37 °C, heart rate 86/minute, blood pressure 140/80 mmHg, respiratory rate 24/minute, and oxygen saturation (SpO2) 99% on room air. He presented with conjunctival congestion, generalized maculopapular rashes, lip swelling, and oral ulcers. The laboratory investigations revealed that the white blood cells (WBC) count was 7640/μL (81.8% neutrophils and 12.3% lymphocytes), hemoglobin (Hgb) was 17.0 g/dL, and the platelet count was 272,000/μL. Additionally, the erythrocyte sedimentation rate (ESR) was 18 mm/hour, and the C-reactive protein (CRP) level was 9.54 mg/L. Liver function tests, cardiac markers, blood urea nitrogen (BUN), creatinine (Cr), albumin, ferritin, fibrinogen, D-dimer levels, and lactate dehydrogenase (LDH) were all within the normal limits (Table 1). The real-time PCR for SARS-CoV-2 were positive.
Complement factors, antinuclear antibodies, immunoglobulins, blood culture, and viral serologies—including those for hepatitis, Ebstein–Barr virus (EBV), herpes simplex viruses 1 and 2, adenovirus, Mycoplasma pneumoniae, influenza A and B, and the human immunodeficiency virus (HIV)—were tested for differential diagnosis to consider autoimmune, rheumatological, and infectious etiologies. No significant abnormalities were detected in the test results. The patient’s clinical course, characterized by diffuse maculopapular rashes and mucosal involvement (Fig. 1), led to the diagnosis of SJS. On the first day of hospitalization, the patient was treated with intravenous immunoglobulin (IG) at 1 g/kg, divided over 3 days and intravenous methylprednisolone 2 mg/kg/day, antihistamines, vitamin C, and dermatological and mucosal care.
After 4 days of intravenous IG and methylprednisolone treatment, the rash and mucosal lesions gradually worsened, with visible blisters on his fingers (less than 10% BSA), ocular pain, photophobia, and erosive lesions on the genital mucosa with exudation (Fig. 2). The dose of methylprednisone was increased to 3 mg/kg/day, and the progression of the patient’s rash and conjunctival lesion was controlled. However, the mucosal erosion and exudation of the external genitalia persisted. The exposed mucosa was treated with sterile isotonic sodium chloride solution for local disinfection and topical application of polymyxin B ointment, and covered with antibacterial dressings until re-epithelialization. The high-dose intravenous methylprednisolone was tapered down, followed by a transition to oral prednisolone. On the 30th day of hospitalization, the patient was discharged without sequelae. After discharge, the patient required a further period of follow-up to ensure full recovery and to monitor potential long-term effects.
Discussion
Stevens–Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is a potentially lethal cutaneous reaction with a mortality rate that can reach up to 30% [7], caused by an immune-complex-mediated hypersensitivity reaction. Most cases of SJS/TEN occur due to drug hypersensitivity [8], often triggered by sulfonamides and anticonvulsants, including phenobarbital, lamotrigine, and carbamezapine [9, 10]. Other drugs, including penicillins, cephalosporins, valproic acid, acetaminophen, and NSAIDs may also pose potential risks as triggers [10]. SJS/TEN generally develops about 4–28 days after initial exposure to the drug [11]. A few cases are related to infections, such as Mycoplasma pneumoniae, group A β-hemolytic Streptococcus, influenza virus, and Ebstein–Barr virus (EBV) [10].
The exact mechanisms underlying SJS/TEN are not fully understood, but it is believed that the diseases are triggered through a T-cell-mediated response. The implicated pathways are thought to involve the Fas–Fas ligand (FasL) or the perforin–granzyme pathways [12]. CD8+T cells and natural killer (NK) cells produce FasL, which binds to Fas on target cells. Recognition of FasL triggers the activation of the caspase cascade, resulting in the apoptosis of the cells. This process contributes to the extensive skin detachment observed in SJS/TEN [13, 14]. In the perforin–granzyme pathways, cytotoxic T cells and NK cells release perforin and granzyme B, which cause keratinocyte damage [15, 16]. Additionally, the secretory granulysin also acts as a primary cytotoxic molecule that leads to disseminated keratinocyte apoptosis in SJS/TEN [17]. The presence of perforin, granzyme B, and granulysin in the early blister fluid is indicative of their role in the disease process, and their concentrations may be correlated with the severity of the condition [17].
During the COVID-19 pandemic, there has been a continuous increase in the number of patients diagnosed with SJS/TEN, with some regions reporting a surge of up to seven times the original amount [18]. This increase correlates with an increase in COVID-19 infections and vaccination rates. Currently, only seven pediatric cases of SJS/TEN associated with COVID-19 have been reported in the literature. Four cases were of TEN, and three were of SJS. Among these cases, six had a history of medication use, with augmentin being the most common. The majority of cases were treated with immunoglobulins and methylprednisolone, and two cases additionally underwent plasma exchange. One case resulted in death due to pulmonary complications; the remaining six cases achieved complete recovery. These cases are summarized in Table 2 [9, 19,20,21,22,23].
Regarding SJS/TENS after COVID-19 infection, it is hypothesized that the generalized immune activation and the associated increase in cytokines induced by COVID-19 infection can directly trigger or render individuals more susceptible to SJS/TEN-inducing type IV hypersensitivity reactions [24, 25]. Additionally, COVID-19 infection can enhance the susceptibility of the skin and mucous membranes to drugs, predisposing patients to drug-induced SJS/TEN [11, 24, 26, 27]. It can also exacerbate existing drug-induced SJS/TEN symptoms [19]. These could explain why children with no prior history of drug allergies develop SJS following COVID-19 infection.
For the treatment of SJS/TEN, rapid withdrawal of the causative drug and intensive supportive care form the basis of the treatment approach. Although there have been reports of positive outcomes with systemic corticosteroids, intravenous IG, cyclosporine, tumor necrosis factor-alpha (TNF-α) antagonists, and plasmapheresis, evidence for systemic therapy remains insufficient [28]. The optimal treatment strategy for SJS/TEN remains controversial.
Our report presents the case of a 15-year-old boy with a recent history of COVID-19 infection and subsequent development of SJS. He has no allergic history. Although our patient did have a history of amoxicillin use prior to the onset of symptoms, our review of previous cases indicates that the role of COVID-19 plays a significant part in the condition.
Conclusions
Stevens–Johnson syndrome (SJS) is a life-threatening condition characterized by high fever and severe mucocutaneous lesions, often triggered by drugs or infection. During the COVID-19 pandemic, there has been a continuous increase in the number of patients diagnosed with SJS/TEN, suggesting a significant association between COVID-19 and the onset of SJS/TEN. The aim of this case report is to raise awareness about the potential for significant COVID-19-induced SJS in the pediatric population and to provide an analysis and summary of the reported pediatric cases. Given that COVID-19 can increase the body’s sensitivity to medications, it is imperative that prescribers exercise caution when selecting and administering drugs. Enhanced surveillance of pediatric patients is crucial during the COVID-19 pandemic to ensure early detection of SJS/TEN symptoms and to facilitate timely therapeutic intervention. Further research is necessary to elucidate the precise mechanisms linking COVID-19 to SJS/TEN and to develop effective prevention and treatment strategies.
Availability of data and materials
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
Abbreviations
- SJS:
-
Stevens–Johnson syndrome
- TEN:
-
Toxic epidermal necrolysis
- IG:
-
Immunoglobulin
- BSA:
-
Body surface area
- COVID-19:
-
Coronavirus disease 2019
- WBC:
-
White blood cells
- Hgb:
-
Hemoglobin
- ESR:
-
Erythrocyte sedimentation rate
- CRP:
-
C-reactive protein
- BUN:
-
Blood urea nitrogen
- Cr:
-
Creatinine
- LDH:
-
Lactate dehydrogenase
- HIV:
-
Human immunodeficiency virus
- EBV:
-
Ebstein–Barr virus
- FasL:
-
Fas–Fas ligand
- NK:
-
Natural killer
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Li, N., Li, J. Coronavirus-disease-2019-associated Stevens–Johnsons syndrome in a 15-year-old boy: a case report and review of the literature. J Med Case Reports 18, 493 (2024). https://doi.org/10.1186/s13256-024-04842-3
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DOI: https://doi.org/10.1186/s13256-024-04842-3