Discussion

Epidermal necrolysis includes Stevens-Johnson syndrome (SJS, <10% of the skin affected), Lyell syndrome (also known as TEN, with ≥30% of the skin affected), and overlap syndrome (10%-29% of the skin affected) [6,7].

The incidence of TEN is estimated at between two and seven cases per million population per year in the general population [8,9]. The absolute risk of SJS/TEN in new users of COX-2 inhibitors is 1.9 cases per 100,000 at first use [10].

According to the literature, TEN tends to occur more frequently in women, with a male-to-female ratio of 0.46 and a predominance in the sixth decade of life [11,12], whereas our patient was a 69-year-old man.

TEN is a delayed hypersensitivity reaction involving drug-specific CD4+ and, especially, CD8+ T lymphocytes after a 7-10-day sensitization phase. Upon re-exposure, these lymphocytes migrate to the skin and trigger keratinocyte death through perforin, granzyme B, granulysin, FasL, TRAIL, and TNF. Granulysin appears to play a central role, with its level in blister fluid strongly correlated with clinical severity. Drug-specific CD8+ T cells, sometimes showing oligoclonal expansion, have been identified in patients with TEN caused by carbamazepine or allopurinol. The first symptoms appeared six days after treatment was initiated. This is consistent with the typical time to onset of the clinical manifestations of TEN (4-28 days) after initiating a medication [1,6].

Clinically, skin involvement is sometimes the first manifestation of the disease, taking the form of ill-defined erythematous macules with purpuric centers or diffuse erythema, which may be tender to the touch. Lesions are often symmetrical, sparing the scalp and the palms and soles of the feet. They often begin on the face and then spread to the chest. There is often a positive Nikolsky sign, followed by the appearance of vesicles and bullae, which subsequently rupture. Mucosal involvement, commonly affecting the oral, ocular, and urogenital areas, is present in approximately 90% of patients. Ocular involvement often manifests as conjunctivitis with purulent discharge, corneal ulceration, anterior uveitis, panophthalmitis, and trichiasis [13-15]. Our patient was admitted with widespread, red, flat patches with skin detachment. Initially, the lesions were mainly on the chest and later spread to the thighs and calves, as shown in Figures 1-3. We also observed conjunctivitis.

The diagnosis is primarily clinical, and the ALDEN imputability algorithm can aid in diagnosis. There are no specific biological markers. Additional tests are conducted to exclude other potential diagnoses or identify accompanying organ dysfunction [6,8].

We performed the minimum emergency laboratory work-up in accordance with the recommendations of the 2023 PNDS (France) for adult epidermal necrolysis. Certain non-specific laboratory abnormalities are also markers of severity, including lymphopenia, hypophosphatemia, hypoalbuminemia, and elevated LDH. This patient had hypoalbuminemia, lymphopenia, and elevated LDH, all of which are markers of poor prognosis.

It is recommended that these patients be admitted to a burns center, even in cases of initially mild disease, as the condition can progress very rapidly [1,16].

TEN is a critical and urgent condition that requires multidisciplinary treatment, with close collaboration between specialists, including dermatologists, resuscitation experts, dietitians, psychiatrists, ophthalmologists, and ear, nose, and throat specialists. There are several aspects to the treatment, the first and most important of which is, of course, the withdrawal of all drugs suspected of having induced TEN. Other measures include dressing; rehydration according to the Brooke Nutrition formula; maintaining the room temperature between 28°C and 32°C; analgesia/anxiolytics; oxygen support or mechanical ventilation if breathing difficulties occur; and infection prevention, including protective isolation, antiseptic cleansing, impregnated catheters, and no routine antibiotic prophylaxis.

To date, supportive care remains equivalent or superior to the therapeutic options already considered, including systemic corticosteroid therapy, intravenous immunoglobulins, cyclosporine, anti-TNF agents, other immunosuppressants, and hematopoietic growth factors [1,6]. Ragragui Ouasmin et al. (2022) and Braud et al. (2023) found these therapies to be beneficial [17,18], whereas Bamichas et al. (2002) and Senda and Fushimi (2024) argued the opposite [19,20].

The overall prognosis of patients admitted to intensive care for multivisceral failure is very poor (mortality 57%) [8]. SCORTEN is used to assess vital risk in the acute phase, and an increase during hospitalization is a poor prognostic factor [1,6]. He had a predicted mortality of 90% with a SCORTEN of 5. He died 48 hours after hospitalization. Although the clinical presentation was highly suggestive, a skin biopsy would have been valuable to help exclude differential diagnoses.

This case underscores the importance of close monitoring and prompt recognition of TEN. Early identification of warning signs, including rapid skin progression, mucosal involvement, or systemic manifestations, is essential. Patients should be instructed to discontinue the suspected drug immediately and seek urgent medical attention.