Case Report: Toxic epidermal necrolysis: a rare pediatric case report from Nepal

Introduction

Toxic epidermal necrolysis (TEN) is a severe potentially life-threatening mucocutaneous reaction, most commonly triggered by medications, characterized by erythematous maculopapular rashes that proceed to diffuse necrosis and exfoliation of the epidermis of the skin.^1,2 TEN is one of several types of severe cutaneous adverse reactions (SCARs), including Steven Johnson Syndrome (SJS), an SJS/TEN overlap, and drug reaction with eosinophilia and systemic symptoms (DRESS).³ The SJS/TEN spectrum encompasses a range of symptoms and severity levels, ranging from mild SJS with less than 10% skin involvement to severe TEN with over 30% skin involvement, with SJS/TEN being intermediate with 10–30% skin involvement.³ The incidence is about 0.4–1.2 cases/million person-years, but the mortality can be as high as 30–40%.² Drugs are the most common cause of TEN, accounting for up to 80% of all cases. Among which cefixime-induced TEN is extremely infrequent (approximately 2%).⁴

The following report describes a case of TEN developed in a six-year-old girl following the intake of cefixime and ibuprofen, which showed significant improvement after supportive care and intravenous corticosteroid therapy.

Case report

A 6-year-old female child from Palpa, Western Nepal, presented in the emergency department of our hospital with fever for four days. It was acute in origin, continuous in character, the maximum temperature noted was 100°F (37.8°C), without chills or rigors, and was accompanied by rashes starting from the postauricular area and facial region and progressed in cephalocaudal direction affecting the upper limb and lower limb. The rashes were accompanied by itching. There was also a history of non-productive, intermittent cough without fast and noisy breathing.

The child was taken to a local hospital, where a diagnosis of measles was made, and prescribed a combination of medications, including syrup cefixime, syrup ibuprofen, paracetamol, syrup fexofenadine, tobramycin eye drops, and calamine lotion. After six hours of taking the medications, the child developed generalized reddish body rashes that eventually resulted in blisters formation and skin peeling. Upon arrival at our emergency department, the rashes covered most of the child’s body. Her eyes were red and discharging. The child also experienced significant loss of appetite since the onset of the illness.

On examination, her vitals were normal except for fever of 101.8°F (38.8°C) and tachypnea (respiratory rate 30 cycles per minute) as per age with normal oxygen saturation in room air. Systemic examination was otherwise unremarkable. On examining the skin, the face, neck, chest, back, and upper and lower limbs showed blisters formation and peeling of skin with positive Nikolsky’s sign. Palms and soles were spared (Figure 1). There was ulceration over the buccal mucosa and cheilitis was present. Ocular examination revealed lesions on bilateral eyelid margins with loss of few lashes, crusting and presence of bleeding point. The conjunctivae were congested and chemosed. The pinnae were tender with multiple erythematous blisters. Genital examination showed ulceration with crusting on the surface of the labia.

Figure 1. Blistering and peeling of skin with sparing of palms.

Laboratory investigations revealed leukopenia of 3,400/μL, and other parameters were within normal range. For further work-up and management, the patient was admitted to the Pediatric Intensive Care Unit (PICU) with strict vitals monitoring and input/output charting. Further management was conducted combinedly with the department of Dermatology, Otorhinolaryngology, Ophthalmology, and Surgery. Swab culture sent to the laboratory revealed Staphylococcus aureus which was sensitive to ciprofloxacin and meropenem. Escherichia coli cultured in urine showed sensitivity to ciprofloxacin, gentamicin and amikacin. The child was treated with maintenance intravenous fluids, antibiotics (meropenem and vancomycin), systemic steroid (dexamethasone), systemic antihistaminic (pheniramine) with appropriate wound and eye care (mupirocin cream, fusidic acid and betamethasone cream, clobetasol and gentamicin cream, lubricating eye drops, ofloxacin eye drops), multivitamin supplements, analgesics (tramadol), and chlorhexidine gargle. Daily cleaning of skin wound with potassium permanganate (KMnO₄) solution and application of vaseline gauge over the exposed areas was done. Fever subsided after a day of admission. Feeding was started via a nasogastric tube (NG) tube on the third day. The oral and skin lesions were gradually regenerating, and the child was started on oral feeds on the ninth day of admission. She was discharged after 12 days of hospital stay as she improved clinically and symptomatically (Figure 2).

Figure 2. Healed skin lesions after treatment.

Discussion

TEN is a dermatological emergency resulting in significant mortality and morbidity. In early stages of the disease, there are a lot of differential diagnoses to be considered but later in the disease course it can usually be diagnosed clinically. In our case, the diagnosis of TEN was made based on the history of drug exposure and the typical manifestation of a generalized reddish rash followed by blister formation and skin peeling involving over 30% of the total body surface area. The prior administration of Ibuprofen and Paracetamol suggests that they are unlikely to be the underlying cause of the observed phenomenon. There was no history of taking any other new drugs, malignancy, systemic illnesses, external chemical exposure, herbal medicines, or new foods. There have been cases of TEN reported in association with viruses like human papillomavirus (HPV) and hepatitis A, but there is no evidence linking measles to the development of TEN.

Although cephalosporins are a rare cause of TEN, our case may have been caused by cefixime. The Naranjo probability score was six suggesting probable drug reaction.⁵ The patient developed the reaction after first dosing of the cefixime. According to the DoTS classification of adverse drug reactions, this adverse reaction could be classified as a “Do” (Dose related) - hypersusceptibility; “T” (Time related) - first dose; “S” (Susceptibility related) - exogenous factor (drugs).⁶ Dechallenge rechallenge testing was not done.⁷ The key to management is early diagnosis and immediate withdrawal of the causative agent, which has been found to improve prognosis. Roujeau et al. reported mortality rate of TEN cases is 25 to 30%.³ The prognosis can be improved by the earlier withdrawal of the causative medication.⁸ Frantz et al. suggested the most effective treatment for the TEN is cyclosporine in combination with corticosteroids with intravenous immunoglobulins (IVIg).⁹ Our case healed completely in twelve days of hospital stay. There is need of further studies to determine the more effective way of management of TEN cases.

Consent

Written informed consent for the publication of the case report and any associated images was sought from the patient’s parent prior to submission.