Cefuroxime-induced toxic epidermal necrolysis in a 4-year-old male child: a case report

Abstract

Introduction:

Toxic epidermal necrolysis (TEN) is a rare, life-threatening mucocutaneous reaction characterized by extensive epidermal detachment and multi-organ involvement. It is most commonly triggered by drugs, including antibiotics such as cephalosporins. Although TEN predominantly affects adults and females, its occurrence in pediatric males is exceedingly rare. Here, we report a fatal case of cefuroxime-induced TEN in a 4-year-old child, emphasizing the importance of early diagnosis, appropriate drug withdrawal, and timely intervention.

Case presentation:

A 4-year-old Pakistani boy presented with persistent high-grade fever, widespread skin desquamation, and mucosal involvement. One month prior, he was prescribed cefuroxime for suspected measles. Within days of initiating therapy, he developed progressive epidermal detachment (>30% of total body surface area), confirming TEN. Laboratory findings revealed anemia, thrombocytopenia, elevated liver enzymes, and markers of systemic inflammation. Despite immediate drug cessation and supportive management, including intravenous fluids, wound care, and mechanical ventilation, his condition deteriorated, leading to multi-organ failure and death.

Discussion:

Cephalosporin-induced TEN is exceptionally rare, particularly in pediatric patients. The pathogenesis involves oxidative stress and keratinocyte apoptosis mediated by TNF-alpha. Treatment primarily consists of supportive care, with emerging therapies such as intravenous immunoglobulin and TNF-alpha inhibitors showing promise. However, limited healthcare resources often hinder access to these interventions in low-income settings.

Conclusion:

This case highlights the fatal potential of TEN, particularly when access to specialized care is limited. Early drug withdrawal and aggressive supportive care remain crucial for improving survival outcomes. Rational antibiotic prescribing is essential to prevent such adverse drug reactions.

Introduction

Toxic epidermal necrolysis is a rare and life threatening disease in which there is detachment of the epidermis along with the involvement of mucosal surfaces^[1]. If proper intervention is not done, it is proven to be fatal. It is caused by exposure to certain medications such as sulfonamides, cephalosporins, penicillins, carbapenems, non-steroidal anti-inflammatory drugs, antiretroviral drugs, corticosteroids, anxiolytics, and anticonvulsants, or infections such as mycoplasma pneumoniae and cytomegalovirus. These inciting agents lead to the detachment of keratinocytes at the dermal-epidermal junction. This causes severe damage to the skin and mucous membranes leading to impending death. As multiple organs continue to be involved, it leads to the dysfunction of eyes, lungs, kidneys, and the hematological system^[2].

HIGHLIGHTS

• Cefuroxime-induced toxic epidermal necrolysis (TEN) is exceptionally rare, especially in a 4-year-old male child.

• Differentiation from other blistering disorders, including Stevens-Johnson Syndrome and Staphylococcal Scalded Skin Syndrome, was critical for accurate diagnosis.

• Financial constraints prevented the use of advanced therapies like intravenous immunoglobulin (IVIG) and TNF-alpha inhibitors, worsening the prognosis.

• Despite supportive care, rapid disease progression led to multi-organ failure and death, underscoring the need for early recognition and accessible specialized treatment.

Toxic epidermal necrolysis has an incidence of 0.4–1.2 per million patients worldwide^[3]. The incidence of Toxic epidermal necrolysis is unknown in Pakistan, whereas Steven-Johnson Syndrome (SJS), which is the milder presentation compared to TEN, has an incidence of 1.89 cases per million per year^[4]. It is more common in females than in males with a ratio of 2:1^[5,6]. Incidence in the pediatric population is 0.4 cases per million worldwide^[7]. We present an extremely rare case of a 4 years-old male pediatric patient of toxic epidermal necrolysis, as toxic epidermal necrolysis is more common in females than in males with the ratio of 2:1, and also it is more common in adult population with the average age is estimated to be 63 years^[5,8].

Case presentation

A 4-year-old Pakistani child presented to the pediatric ward with complaints of a non-resolving high-grade fever and a worsening rash. One month prior, he was diagnosed with measles by his family physician and prescribed cefuroxime, a second-generation cephalosporin. Shortly after initiating the antibiotic, it was reported that he developed skin desquamation (Fig. 1), initially localized to his face (9%) and the anterior aspect of both legs (18%). This gradually worsened over time. At admission, he had high-grade fever (up to 104°F) and episodes of vomiting. There was no history of previous drug allergies, and his family history was unremarkable. On physical examination, he appeared alert but febrile with generalized body edema. A positive Nikolsky’s sign was noted, with areas of the skin peeling off upon slight pressure.

Figure 1.

Initial presentation of the patient. A: Desquamation of the skin of face including lips, chest and abdomen. B: Desquamation of the skin of the left arm and hand. C: Bilateral desquamation of the skin of arms and hands. D: Swollen edematous feet and desquamation of the skin of feet.

The patient received cefuroxime immediately after the measles diagnosis and began developing symptoms within 3–5 days. The drug was discontinued one month later upon hospital admission.

Stevens-Johnson Syndrome (SJS) was initially considered due to the history of drug exposure and cutaneous manifestations. However, it was ruled out based on the extent of epidermal detachment (>30% body surface area), which is consistent with Toxic Epidermal Necrolysis (TEN). Unlike TEN, SJS typically involves <10% of the body surface area. Other potential differentials such as Staphylococcal Scalded Skin Syndrome (SSSS) and Toxic Shock Syndrome (TSS) were considered. However, SSSS was excluded due to the lack of mucous membrane sparing, age group predominance (SSSS is more common in infants), and absence of exfoliative staphylococcal toxins in bacterial cultures. Similarly, TSS was ruled out as no evidence of hypotension, organ dysfunction, or causative bacterial source was found. The diagnosis of TEN was confirmed via histopathological examination of a skin biopsy, which revealed full-thickness epidermal necrosis with subepidermal detachment.

The patient’s laboratory investigations revealed anemia with hemoglobin levels of 11.5 g/dL (normal: 12–16 g/dL), eosinophil percentage of 0.022% (normal: 1–4%), neutrophil count of 3.12/mm³ (normal: 2.5–7.5/mm³), lymphocyte count of 2.87/mm³ (normal: 1.5–4.0/mm³), and a low platelet count of 79.1 × 10³/mm³ (normal: 150–400 × 10³/mm³). Liver function tests were deranged, showing elevated ALT of 400 U/L (normal: <40 U/L), AST of 243 U/L (normal: <40 U/L), and ALP of 260 U/L (normal: 44–147 U/L), while albumin was reduced to 2.83 g/dL (normal: 3.5–5.0 g/dL). Urinalysis revealed raised pus cells (2–3). Additional investigations showed elevated levels of creatine phosphokinase (CPK), lactate dehydrogenase (LDH), and C-reactive protein (CRP), further supporting the diagnosis of TEN.

Cefuroxime was immediately discontinued. The patient received supportive care, including intravenous fluids for hydration and electrolyte balance, paracetamol for pain relief, and miconazole oral gel for oral lesions. Due to hypoxemia with oxygen saturation dropping to 90% on room air, mechanical ventilation was initiated. Advanced therapies, including intravenous immunoglobulin (IVIG), TNF-alpha inhibitors, and plasmapheresis, were considered but could not be initiated due to financial constraints. Cyclosporine and high-dose corticosteroids, which are cost-effective treatments, were also unavailable at the facility. Supportive care included wound care with sterile dressings, hemodynamic monitoring, and nutritional support, though this was limited by the patient’s critical condition.

Despite supportive treatment, the patient’s condition worsened. Within 3 days of admission, desquamation extended to both arms bilaterally (18%) and the anterior chest and abdomen (18%), covering 63% of the total body surface area (Fig. 2). Mucosal involvement of the oral cavity was observed, further complicating his nutritional intake. By the fifth day, the patient developed disseminated intravascular coagulation secondary to sepsis, which led to multi-organ failure and ultimately his death.

Figure 2.

Presentation of the patient 3 days after admission. Extensive desquamation of the scalp, face, neck, chest and both arms could be seen. The abdomen, legs and feet were also affected but the parents of the patient only allowed imaging of the child in a clothed state.

This tragic case highlights the critical need for early diagnosis, timely cessation of the offending drug, and access to advanced treatments for managing TEN in resource-limited settings. While advanced therapies may not guarantee survival, they could offer a better prognosis in severe cases like this.

Discussion

Extensive exfoliation of the mucous membrane and epidermis is a potentially fatal manifestation of toxic epidermal necrolysis (TEN), which can lead to sepsis and death^[9]. Steven-Johnson Syndrome (SJS) is thought to fall within the same range of drug-induced epidermolysis and exhibits similar clinical processes. The extent of skin detachment is the primary distinction. SJS often affects less than 10% of the body’s surface area, whereas TEN typically involves more than 30% of it^[10].

Cefuroxime induced TEN is rarely reported in literature. Grgurević et al reported a case of cefuroxime induced toxic epidermal necrolysis in a 73 years old woman that despite intensive treatment was fatal^[11]. Although their patient was significantly older than our patient, Lam A et al reported a case of an 84-year-old man who experienced toxic epidermal necrolysis (TEN) as a result of ceftriaxone^[12]. In terms of age and gender, Babu et al’s case of cefixime-induced TEN in a 7-year-old boy is more consistent with the appearance of cephalosporin-induced TEN observed in our patient^[13].

One theory for the pathophysiology of TEN is oxidative stress. In keratinocytes, glutathione S-transferase-p (GST-p) is a biomarker of oxidative stress. In comparison to other cutaneous medication reactions, TEN patients have been found to have a greater level of this marker^[14]. Reactive oxygen species (ROS) can build up as a result of a culprit medicine interfering with detoxification mechanisms, which can lead to programmed cell death.

The early blistering and painful eruption of cutaneous lesions is the hallmark of the clinical presentation of TEN. In most cases, mucous membrane involvement occurs before skin lesions. This eruption primarily affects the trunk and proximal limbs and spreads symmetrically from the face and upper body to the entire body^[15].

Systemic steroids, plasmapheresis, cyclosporin, anti-tumor necrosis factor-alpha (TNF-alpha), and intravenous immunoglobulin (IVIG) are among the therapeutic modalities that are yet to be demonstrated to be effective^[16]. However, Saavedra et al described a case of toxic epidermal necrolysis caused by cephazolin that responded well to intravenous immunoglobulin and N-acetylcysteine treatment^[17].

In skin lesions, TNF-alpha is overexpressed in the keratinocytes that are affected and this expression is particularly high in skin blisters. TNF-alpha inhibitors are reported in some studies to cause skin lesions to resolve swiftly. When administered over the first 48 to 72 hours, IVIG likewise showed positive outcomes^[18]. Although antibiotics such as sulfonamides are more commonly implicated, cephalosporins like cefuroxime have also been reported, albeit rarely. Comparative studies suggest that sulfonamides, anticonvulsants, and NSAIDs are among the leading drug classes associated with TEN, while cephalosporin-induced cases represent a minority^[2]. Cefuroxime, like other beta-lactam antibiotics, is hypothesized to act as a hapten, modifying self-proteins and triggering a cytotoxic T-cell response. TNF-α plays a central role in this immune cascade, inducing apoptosis of keratinocytes via Fas-FasL interaction and promoting inflammation. The elevated TNF-α in blister fluid further supports its involvement in TEN pathophysiology^[19]. In resource-limited settings, early initiation of systemic corticosteroids remains controversial but may offer benefits if started within 48 hours of onset. Cyclosporine, an affordable immunomodulator, has shown potential in halting disease progression in some case series. Basic wound care, nutritional support, and infection prevention are critical low-cost interventions that can be optimized even in under-resourced facilities^[2,19].

Conclusion

This case highlights the urgent need for antibiotic stewardship, particularly in pediatric settings, and highlights the inequities in access to advanced dermatological care. Public health policies aimed at regulating antibiotic use and investing in accessible treatment options for severe dermatologic emergencies are imperative. Even though early detection and removal of the offending medicine are crucial first steps, the survival of the patient depends on rapid access to specialist care, such as intensive care units (ICU) or burn centers, and advanced therapies like intravenous immunoglobulin (IVIG) or plasmapheresis. Unfortunately, the lack of financial resources hindered the child’s access to optimal care, leading to a fatal outcome.

Ethical approval

Ethical approval is not required for the case report in our institution, Nishtar Medical University.

Consent

Written informed consent was obtained from the patient’s parents/legal guardian for publication and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request.

Sources of funding

Not applicable.

Author contributions

A.K., Q.A, and A.B.: conceptualized the study, curated data, and conducted the investigation; A.K., Q.A., M.A.A., and A.B.: wrote the original manuscript; A.K., A.B., M.K., and M.A.: reviewed and edited the manuscript; A.K. and M.A.: administered the project; M.A.: supervised the study.

Conflicts of interest disclosure

The authors declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Guarantor

Mohamed Antar.

Research registration unique identifying number (UIN)

Not applicable.

Provenance and peer review

All the relevant data have been included in the manuscript itself.

Data availability

All the relevant data have been included in the manuscript itself.