An 80-year-old woman with adenocarcinoma (cT4N0M1c [BRA, PUL], stage VIB) and harboring an EGFR-sensitizing mutation (L858R) was treated with osimertinib in December 2018 as the first-line treatment, which led to a partial response with marked tumor shrinkage, which was assessed by chest computed tomography after 3 weeks of osimertinib treatment in January 2019. Erythematous papules were observed on the anterior chest wall 32 days after osimertinib induction. Therefore, the patient was referred to the department of dermatology of our institution. Since the dermatologic adverse event (AE) was diagnosed as mild at that time, a topical corticosteroid ointment was prescribed without cessation of osimertinib treatment. However, diffuse erythematous rash rapidly spread over the patient’s trunk (A) and was accompanied by vesicles and purpuric macules; furthermore, targetoid erythema developed on her face (B) after 14 days. Therefore, osimertinib was immediately discontinued. However, the erythema and macules did not alleviate after osimertinib discontinuation and oral prednisolone at a dose of 30 mg was initiated 5 days after osimertinib discontinuation. Four days after the initiation of prednisolone, diffuse erythema with Nikolsky’s sign, general epidermal detachment, erosion and loose blisters developed over her entire body including the face (C). Based on these symptoms, a clinical diagnosis of TEN was made, which was supported by a skin biopsy showing acute interface dermatitis with eosinophil infiltration (D). Therefore, intravenous immunoglobulin (IVIG; 15 g/day) was immediately administered for 4 days. Ten days after IVIG treatment, the erythematous rash on the patient’s trunk disappeared and some scar lesions remained (A). Furthermore, general epidermal detachment, erosion and loose blisters on her face ameliorated with epithelialization (B). Therefore, oral prednisolone was gradually tapered off.
In October 2017, a 51-year-old man, suffering from loose blisters, large-area skin peelings (nearly involving the entire body), mucosal erosion and fever, visited The First Affiliated Hospital with Nanjing Medical University. He had been diagnosed with stage IV EGFR-mutation-positive advanced NSCLC with pleural metastasis in 2016 and received treatments at a thoracic hospital regularly. After chemotherapy (pemetrexed plus cisplatin for six cycles) was completed, icotinib continued to be used till August 2017 when the drug resistance was revealed. Once EGFR T790M mutation was diagnosed, he started taking AZD-9291 with a dose of 80 mg/day to delay the disease progression. Twenty-one days later, he presented with several oral blisters and scattered erythematous maculopapular rashes, which rapidly developed into mucosal erosion and general epidermal detachment involving his entire body with exfoliation on his back skin (). When admitted into our department, he was unable to get up owing to severe pain, extreme feebleness, fever, and lower limb edema.