Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but severe acute mucocutaneous reactions characterized by extensive epidermal detachment, mucosal erosions, and potential multiorgan dysfunction, including hepatic, renal, and pulmonary complications [1,2]. These conditions are classified based on the extent of skin involvement: SJS involves less than 10% of the body surface area, TEN more than 30%, and cases with 10%–30% involvement are categorized as SJS/TEN overlap [3].

TEN is associated with a high risk of systemic complications and can significantly prolong recovery by affecting major organs such as the liver, kidneys, and lungs [4]. Globally, SJS/TEN imposes a substantial clinical and economic burden due to prolonged hospitalization, high mortality rates, and the potential for long-term physical, psychological, and multisystemic sequelae [5]. Amoxicillin and macrolides, which are among the most commonly used antibiotics in first-line Helicobacter pylori eradication therapy, have both been rarely associated with the development of SJS/TEN [6,7].

We report a fatal case of SJS/TEN in an 80-year-old woman who developed acute kidney injury and refractory hypotension after receiving standard triple therapy for H. pylori infection.

An 80-year-old woman presented to the emergency department with a 14-day history of melena. The patient had a medical history of hypertension, osteoporosis, and peptic ulcer disease three years earlier. There were no specific findings in family or social history. The patient had no specific history of allergies, and prior exposure to penicillin or macrolide could not be confirmed. Upper gastrointestinal endoscopy showed an approximately 1.5 cm flat and superficial vessel exposure located on the lesser curvature of lower body, with marked touch bleeding upon endoscopic contact (Fig. 1). The patient was admitted and treated with intravenous proton pump inhibitors (PPIs). The patient was discharged after 5 days with no recurrence of bleeding.

Two weeks after discharge, the patient visited outpatient clinic. The serum anti-H. pylori IgG was confirmed to be positive, and the patient was prescribed with a standard triple therapy consisting of pantoprazole 40 mg BID, amoxicillin 1 g BID, and clarithromycin 500 mg BID. Four days after initiating therapy, the patient returned to the emergency department with complaints of low-grade fever, generalized pruritus, and bullous skin eruptions with desquamation localized to the right axilla, abdomen, and perineum (Fig. 2). The patient was admitted to the department of allergy.

At the time of presentation, vital signs were as follows: blood pressure 70/40 mm Hg, heart rate 90 bpm, respiratory rate 20 breaths/min, and body temperature 37.7°C. The patient was alert and oriented. Due to hypotension, norepinephrine was administered. The patient complained of intense pruritus and diffuse skin lesions. Laboratory results revealed a white blood cell count of 7210/uL (ref: 4000–10000/uL) with a differential of 93.4% neutrophils (ref: 40%–74%) and 0.3% eosinophilis (ref: 0%–7%); aspartate aminotransferase 46 U/L (ref: 0–35 U/L), alanine aminotransferase 20 U/L (ref: 0–35 U/L), lactate dehydrogenase 327 U/L (ref: 120–250 U/L), creatinine 1.23 mg/dL (ref: 0.6–1.2 mg/dL), hemoglobin 10.4 g/dL (ref: 12–16 g/dL), and C-reactive protein 95 mg/L (ref: 0–5 mg/L). All viral markers were negative. Abdominal computed tomography showed no significant findings. The skin lesions covered less than 10% of the total body surface area, and SJS was clinically suspected. The patient was admitted to the intensive care unit.

The suspected medicine, amoxicillin/clarithromycin, were withdrawn. The patient’s regular medications included dexibuprofen, teriparatide, rebamipide, and tramadol; however, as these were not recently initiated, an association with SJS/TEN was not considered. Initial treatment included intravenous fluid resuscitation, antibiotics, and methylprednisolone 20 mg BID. Wound care with full-body dressing was also initiated. Despite treatment, the skin lesions progressed, and widespread epidermal detachment involving more than 30% of the body surface area was observed. Finally, the patient was clinically diagnosed with TEN. On hospital day 17, the patient developed candidemia, which rapidly progressed to multiorgan failure and resulted in death on hospital day 20.

H. pylori infection is a well-established etiologic agent in chronic antral gastritis, peptic ulcer disease, mucosa-associated lymphoid tissue lymphoma, and gastric adenocarcinoma [8]. Various antibiotic regimens have demonstrated high efficacy and safety in the eradication of H. pylori [9]. Korean guideline recommend a 14-day standard triple therapy consisting of clarithromycin 500 mg twice daily, amoxicillin 1 g twice daily, and a PPI at standard dose twice daily as the first-line treatment [10].

However, the concomitant use of two antibiotics increases the likelihood of adverse effects. These side effects may significantly reduce medication adherence and subsequently contribute to treatment failure.

In rare instances, cutaneous hypersensitivity reactions can occur during eradication therapy. A prior study demonstrated that most cutaneous reactions appear within the first three days of therapy, with urticaria, angioedema, and maculopapular eruptions being the most common presentations [11]. Notably, the majority of mild cutaneous manifestations resolve without requiring discontinuation of the antibiotics [11]. These reactions are believed to be mediated via non-IgE-dependent mast cell activation mechanisms [11]. Despite their generally favorable safety profiles, amoxicillin and macrolides have been implicated in rare but severe cutaneous adverse reactions, including SJS and TEN [2]. In a meta-analysis of 38 studies conducted worldwide, antibiotics accounted for approximately 28% of drugs implicated in the onset of SJS/TEN [12]. Among these, sulfonamides comprised 32%, penicillins 22%, cephalosporins 11%, fluoroquinolones 4%, and macrolides 2% [12]. Definitive evidence that concomitant use of multiple antibiotics independently increases the risk of SJS/TEN is currently lacking, and the risk appears to be primarily determined by the individual agents involved [13]. These reactions most commonly occur within four weeks of initiating therapy; in our case, clinical features were evident within four days. The pathophysiology of SJS/TEN is presumed to be immune-mediated, wherein drugs interact with cellular and human leukocyte antigen receptors, provoking an exaggerated immune response. Subsequent infiltration by CD8+ cytotoxic T lymphocytes and natural killer cells leads to keratinocyte apoptosis and extensive epidermal necrolysis [5,14].

Management of SJS/TEN involves prompt cessation of the offending agent and the initiation of intensive supportive care. A multidisciplinary team approach, involving dermatology, ophthalmology, plastic surgery, and specialized wound care nurses, is critical for optimal patient outcomes. Admission to an intensive care or burn unit is often necessary [1]. Core elements of supportive care include meticulous wound management, fluid and electrolyte replacement, hemodynamic stabilization, and adequate analgesia. Although corticosteroids, intravenous immunoglobulin, and cyclosporine have been used in clinical practice, no standardized therapeutic protocol has yet been established [1].

Although SJS/TEN may occur at any age, mortality rates are notably higher among older adults [15]. In elderly patients, it is essential to balance the therapeutic benefits of H. pylori eradication with the potential risks. However, eradication efficacy and the frequency of adverse events did not significantly differ between elderly and younger populations, suggesting that age alone should not be considered a contraindication for therapy [16]. Maastricht VI consensus also states that H. pylori eradication offers the chance for gastric cancer prevention at any age in adulthood and the magnitude of the benefit decreases with age [8]. Therefore, individualized risk–benefit assessment and close monitoring are particularly important when initiating eradication therapy in elderly patients.

While SJS/TEN can occur even in patients without a known penicillin allergy, thorough screening for drug hypersensitivity— especially to penicillin—remains essential to ensure the safety of eradication therapy [17]. Detailed pre-treatment history taking and documentation should be routine practice. To facilitate this, the implementation of structured programs and electronic systems for allergy history management is warranted. Additionally, raising awareness among healthcare professionals regarding potential severe drug reactions is essential for improving safety, enhancing treatment success, and reducing unnecessary healthcare expenditures.

In summary, this case highlights the rare but serious risk of SJS/TEN associated with standard H. pylori eradication therapy. As H. pylori eradication therapy continues to expand and treatment becomes more widely implemented, especially in elderly patient, clinicians should be aware of the potential adverse drug reactions and provide appropriate patient education prior to treatment. A proactive, risk-stratified approach, underpinned by multidisciplinary collaboration and structured monitoring systems, is key to maximizing therapeutic safety and efficacy across all patient populations, including the elderly.