Sintilimab, a humanized anti-PD-1 monoclonal antibody, has demonstrated significant efficacy in the treatment of advanced non-small cell lung cancer (NSCLC) by enhancing T-cell immune responses (Zhang et al., 2022). However, similar to other immune checkpoint inhibitors (ICIs), it can cause severe immune-related adverse events (irAEs), including toxic epidermal necrolysis (TEN) (Satoh et al., 2023). TEN is a life-threatening type IV hypersensitivity reaction characterized by widespread epidermal necrosis and detachment, affecting more than 30% of the total body surface area (BSA) (Singh and Phillips, 2022; Hinc-Kasprzyk et al., 2015). TEN can lead to serious complications such as infections, electrolyte imbalances, and organ failure, with a mortality rate of up to 40% (Singh and Phillips, 2022; Hinc-Kasprzyk et al., 2015; Sorrell et al., 2017).

Despite extensive use of Sintilimab in NSCLC management (Zhang et al., 2022), reports of TEN associated with this agent remain exceedingly rare, with only three documented cases in the literature to date (Jiang et al., 2023; Li et al., 2022; Lye et al., 2023) (Supplementary Table S1). This case provides novel insights through: (1) First documentation of TEN after re-initiation of Sintilimab (second exposure a year apart) with the shortest latency period (72 h post-infusion) reported to date; (2) Demonstration of successful management in a patient with up to 85% BSA involvement; (3) Comprehensive longitudinal tracking of mucosal and systemic manifestations. Our experience underscores the imperative for early recognition algorithms and standardized management protocols in ICIs-associated TEN.

The patient was a 60-year-old Asian female. In February 2023, she was diagnosed with centrally located lung squamous cell carcinomas (T4N2MX). Immunohistochemical staining showed CK (+), BRG1 (+), CK5/6 (+), P40 (+), TTF-1 (−), NapsinA (−), Syn (−), Ki-67 (50% +).

She received four cycles of chemotherapy with paclitaxel and carboplatin, but due to disease progression, the regimen was switched to docetaxel, cisplatin, plus Sintilimab in June 2023. After one cycle of the combined therapy, the patient developed severe gastrointestinal reactions and opted for voluntary discharge. She did not continue with regular follow-up care thereafter. There were no obvious side effects related to rash during the treatment performed above.

On 28 February 2024, the patient was re-admitted with complaints of lower back pain and right lower limb weakness. She was diagnosed with stage IV lung squamous cell carcinoma with liver, bone, and cervical lymph node metastasis (cT4N3M1).

After admission, palliative radiotherapy was administered to the lumbosacral region due to bone metastases, with 13 sessions from March 5 to 21 March 2024. On March 25, palliative radiotherapy was extended to the nasal mass and cervical lymph nodes. The treatment regimen also included oral vinorelbine (60 mg) and Sintilimab (200 mg).

Palliative radiotherapy was administered to the lumbosacral region (March 5–21) and later to the nasal mass and cervical lymph nodes (starting March 25) (Supplementary Table S2). Concurrently, oral vinorelbine (60 mg) and sintilimab (200 mg) were initiated on March 25.

On March 28, 3 days after receiving Sintilimab, scattered erythematous maculopapular eruptions first appeared on the patient’s lower back and arms. Given the localized distribution and mild nature of the rash, clinical assessment favored continuing the planned palliative radiotherapy. The following day (March 29), the cutaneous eruption progressed, with similar lesions appearing on the face and neck, accompanied by bilateral conjunctival redness, which is a recognized manifestation of ICIs-associated TEN (Ma et al., 2021). At this point, radiotherapy was halted. Subsequently, the patient’s condition deteriorated rapidly, with the rash spreading over most of her body, accompanied by high skin temperature and severe itching (Figures 1A–D).

From 4 April 2024, the rash had covered approximately 60% BSA, with large blisters forming and some epidermal detachment affecting about 11% BSA. Methylprednisolone (160 mg/day) and intravenous cefuroxime were administered for anti-inflammatory and infection prevention purposes. The condition continued to deteriorate, with the rash extending to 70%–80% BSA and more extensive epidermal detachment (≥18% BSA) by April 8–9 (Figure 2A), leading to painful oral and nasal mucosal erosion.

From April 10 to April 15, generalized rash, bullae, and epidermal detachment involved approximately 85% BSA, with epidermal sloughing accounting for approximately 35% BSA (Figures 2B–D). Intensive wound care, immunoglobulin therapy, and high-dose corticosteroids were continued. Culture tests from blister fluid and exudates revealed Escherichia coli infection, which was treated with meropenem.

By April 18 (24 days post-Sintilimab injection), skin redness, edema, and pain gradually improved, and new skin growth was observed on the face, neck, and back (Figures 3A,B). By April 25, the areas of epidermal sloughing had reduced to about 40% BSA, with significant recovery of the original skin appearance and function in many regions (Figures 3C,D). Lower extremity edema persisted but improved with diuretic therapy.

On 6 May 2024 (42 days post-Sintilimab injection), the patient’s skin had almost completely recovered (Figure 4), and she was discharged in stable condition. During a follow-up visit 3 months later, the patient remained in good health with no new skin lesions or long-term complications. A timeline of major treatments during admission is presented in Supplementary Figure S1. Representative CT scans demonstrating tumor changes are presented in Supplementary Figures S2, S3. Changes in major laboratory indicators during admission is presented in Supplementary Table S3.

Informed consent was obtained from the patient before the submission of this case report for publication including the use of images. Ethical approval for this report was obtained from the ethics committee of SINO SINGAPORE CANCER CENTRE.

This case confirms the potential of Sintilimab, a widely used PD-1 inhibitor, to induce life-threatening TEN, even with a favorable antitumor response. It underscores that early recognition, immediate drug cessation, and aggressive supportive care—including immunomodulation and meticulous wound management—are critical for survival. This report highlights the severe risk-benefit dilemma that can arise with ICIs. Further research is needed to identify predictive biomarkers and optimize management protocols for such rare but fatal irAEs.