Co‐Trimoxazole‐Induced Toxic Epidermal Necrolysis: A Case Report From Nepal

ABSTRACT

Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe mucocutaneous reactions, often triggered by medications, characterized by blistering and epithelial sloughing. We report the case of a 66‐year‐old male who presented with a 2‐day history of fluid‐filled lesions on his body. On examination, erosions were observed on the posterior and anterior trunk, as well as on both upper and lower limbs. Multiple vesicles and bullae were scattered bilaterally, involving 60%–70% of the body surface area. Co‐trimoxazole‐induced SJS was diagnosed. The patient was admitted to the ICU and treated with dexamethasone, hydrocortisone, imipenem, and azithromycin. Corticosteroids, combined with broad‐spectrum antibiotics, were effective in managing the condition. Early intervention and a multidisciplinary approach helped prevent complications and secondary infections.

Summary.

• Co‐trimoxazole‐induced Stevens–Johnson syndrome (SJS) complicated by toxic epidermal necrolysis (TEN) requires early recognition and prompt intervention, particularly in genetically susceptible individuals, to prevent severe complications and mortality.

1. Introduction

Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are among the most life‐threatening conditions managed by dermatologists, characterized by the detachment of necrotic epidermis and mucosal membrane erosions, often accompanied by a positive Nikolsky sign [1, 2]. Nikolsky sign is elicited by applying tangential or lateral pressure with a thumb or finger to the perilesional, affected, or even normal skin, causing the upper layers of the epidermis to dislodge from the lower layers [3].

Mucosal involvement, seen in approximately 80% of cases, is a hallmark of SJS/TEN [2]. These conditions share a common pathophysiology and are classified on the basis of the extent of body surface area (BSA) affected: < 10% BSA involvement defines SJS, 10%–30% indicates overlap syndrome, and > 30% constitutes TEN [4]. A study by Yang et al. [5] reported the incidence of SJS and TEN to be 1.0–6.0per million and 0.4–1.2 per million, respectively, with rates being approximately twofold higher in the Asian population.

The prevalence of SJS and TEN due to drug reactions is very rare. Co‐trimoxazole, a sulfonamide‐class antibiotic, is a combination of sulfamethoxazole and trimethoprim, commonly used to treat various bacterial, fungal, and protozoan infections [6]. The risk of developing SJS due to co‐trimoxazole is estimated at one case per million people per year [7]. Here, we present a case of SJS complicated by TEN, triggered by co‐trimoxazole.

2. Case Report

2.1. Case History

A 66‐year‐old male presented to the dermatology department with a 2‐day history of fluid‐filled lesions over his body. Seventeen days prior, he developed fever, vomiting, and burning micturition and was prescribed co‐trimoxazole DS (160/80 mg) for 6 days, suspecting a urinary tract infection (UTI). His symptoms initially improved but recurred, leading to another course of co‐trimoxazole for unresolved UTI. After 2 days of this second treatment, the patient experienced an unusual sensation of erythema and itching over his entire body, followed by the formation of a pea‐sized blister on his left forearm (Figure 1). Within 3–4 h, the blister increased in size and began spreading to his left arm, right upper limb, and the trunk, eventually affecting his lips, face, and scrotal region. The blisters ruptured spontaneously, leading to watery discharge, red areas, and peeling of the skin. He also developed redness and discharge in both eyes, along with photophobia, burning, and pain. Peeling of his lips with a pale yellow viscous discharge and associated difficulty in eating and swallowing was noted. The skin detachment initially involved < 15% of his BSA but increased to 60%–70% within a week. The patient had a history of diabetes mellitus, hypertension, and nephrotic syndrome, for which he was receiving treatment.

FIGURE 1.

Blisters present on the left forearm of the patient.

2.2. Physical Examination

On cutaneous examination, 15% of his BSA was involved at the time of presentation, increasing to 70% within 1 week (Figures 2, 3, and 4). There were erosions on his posterior trunk, including a 10 × 5 cm lesion on the left side, with similar erosions on the chest and trunk (Figures 2 and 3). Multiple vesicles and bullae were distributed across his upper and lower limbs, with erosion and yellowish‐white slough in the angles of his mouth. Bilateral conjunctival redness was more prominent in the right eye, accompanied by multiple discrete erosions in the periorbital area. Erythema, slough, and erosions were present on the scrotum and penis. Nikolsky's sign was positive, and the patient's severity of illness score of toxic epidermal necrolysis scale (SCORTEN) was 1 at presentation. The SCORTEN is a prognostic tool used to assess mortality risk in SJS/TEN patients, with seven components each contributing one point: age > 40 years, heart rate > 120 beats/min, presence of malignancy, BSA detachment > 10%, serum urea > 10 mmol/L, serum glucose > 14 mmol/L, and serum bicarbonate < 20 mmol/L. Our patient had a SCORTEN score of 1 because of his age (66 years).

FIGURE 2.

Peeling of skin and erosions on the back of the patient.

FIGURE 3.

Erosions on the chest and anterior trunk of the patient.

FIGURE 4.

Erosions extending in the face region of the patient.

2.3. Laboratory Investigations

Investigations revealed hemoglobin levels of 9.9 g%, a total leukocyte count of 7000/cumm, platelets at 126,000, ESR at 54 mm/h, and a blood urea/creatinine ratio of 38.9/0.9 mg/dL. Electrolytes showed sodium at 128 mEq/L and potassium at 3.93 mEq/L. Urinalysis showed albumin (+), glucose (+), 1–2 pus cells/HPF, and 3–5 epithelial cells/HPF. Spot urine tests showed a protein/creatinine ratio of 2.11.

2.4. Management

Because of deranged renal function, the patient was admitted to the ICU. He was managed with intravenous (IV) imipenem and cilastatin (500 mg/500 mg) BD for 2 days, then QID for 12 days, along with azithromycin 500 mg for 3 days. IV dexamethasone was administered in a tapering dose for 12 days, along with hydrocortisone 100 mg TDS for 4 days. Filgrastim 300 μg was also given. The patient was placed on an insulin sliding scale and continued on amlodipine because of his diabetes and hypertension. Topical treatments included candid mouth paint, betamethasone for oral mucosa, Vaseline petroleum jelly for the lips, and ofloxacin and ciprofloxacin eye drops with refresh tears for eye care. Mupirocin and Vaseline jelly were applied to skin lesions. Initial dietary modifications to a soft, high‐calorie diet proved insufficient, and enteral feeding was initiated through a nasogastric tube.

2.5. Outcome and Follow‐Up

Swab cultures were negative, and the patient recovered steadily. The patient was regular on his follow‐ups and showed improvement.

3. Discussion

In developed countries, the incidence of acute cutaneous drug reactions among inpatients ranges from 1% to 3%, whereas in developing countries, it is between 2% to 5% [8]. Antimicrobials (50%), nonsteroidal anti‐inflammatory drugs (22.41%), and antiseizure drugs (18.96%) are the most commonly associated drug classes [9]. Among high‐risk drugs, anti‐seizure medications are the most frequent cause of TEN, with an 81.8% likelihood of triggering severe eruptions, compared with NSAIDs (53.84%) and antimicrobials (34.48%) [9]. Although co‐trimoxazole‐induced SJS is not among the most common causes, there are reported cases of this association [1]. Our patient received co‐trimoxazole for 6 days during his initial presentation and for 2 days during the second presentation for unresolved UTI.

Cutaneous and mucosal involvement is a hallmark feature of SJS/TEN, typically beginning as erythematous macules on the trunk that progress to dusky areas with surrounding erythema and a positive Nikolsky sign [10]. Our patient also presented with bilateral mucosal involvement, including yellowish‐white slough at the angles of the mouth. A study by Charlton et al. [10] indicated that 90% of cases involved oral and genital mucosa, with complications such as shedding of epidermal surfaces, including the oral mucosa, cornea, and scrotal skin. Furthermore, about one‐third of SJS/TEN patients have genitourinary involvement, a finding also present in our case [10]. The average hospital stay is reported to be 9.7 days for SJS, 20.6 days for TEN, and 16.1 days for SJS–TEN overlap syndrome [9]. Our patient required a 26‐day hospital stay, which was longer than average.

Genetic susceptibility to SJS/TEN is linked to the HLA‐B*38:02 allele, a variant of the HLA‐B gene, which has a well‐established association with co‐trimoxazole‐induced SJS/TEN [11]. The severity of illness in TEN is assessed using the SCORTEN score, first proposed in 2000, which helps determine prognosis based on factors such as skin detachment [12]. Our patient's SCORTEN score was 1, warranting ICU admission. He had several poor prognostic factors, including nephrotic syndrome and diabetes mellitus.

Treatment included IV and topical steroids, antibiotics, IV fluids, and regular dressing changes. Imipenem was used as a broad‐spectrum antibiotic, whereas azithromycin was administered to cover atypical organisms. The decision to use corticosteroids is based on their ability to modulate the immune response, which is often beneficial in severe cases. The most crucial aspect of managing SJS/TEN is the early identification and withdrawal of the offending medication. Complications, particularly secondary infections, occur more frequently in the TEN group (63.4%), with a reported mortality rate of 26.66% [8]. Despite involving 70% BSA with mucosal involvement, our patient survived.

4. Conclusion

SJS/TEN due to co‐trimoxazole can occur in genetically susceptible individuals, making it essential to closely monitor clinical changes as hypersensitivity reactions may develop rapidly. Early identification and timely intervention are vital to prevent complications and secondary infections, especially in cases involving extensive BSA and mucosal complications. Screening for the HLA‐B*38:02 allele and proper patient counseling can significantly reduce the risk of developing this life‐threatening condition.

Author Contributions

Sandesh Gaire: conceptualization, data curation, validation, visualization, writing – original draft, writing – review and editing. Suchit Thapa Chhetri: conceptualization, data curation, validation, visualization, writing – original draft, writing – review and editing.

Consent

Written informed consent form was obtained from the patient to publish this report in accordance with the journal's consent policy.

Conflicts of Interest

The authors declare no conflicts of interest.

Data Availability Statement

All the findings are present within the manuscript.