A 42-year-old woman diagnosed with stage IV NSCLC (adenocarcinoma) was admitted to our hospital in August 2013 and given an AP regimen (pemetrexed 500 mg/m2 on day 1, cisplatin 75 mg/m2 on days 1 to 3, repeated every 3 weeks) as initial chemotherapy on August 2nd, 2013. She received folate, vitamin B12, and corticosteroids as recommended. Several days later, her EGFR genetic test results demonstrated an exon 19 mutation (L747-T751>P); thus, she started taking gefitinib (250 mg once daily) on August 15th. On August 23th, which was 21 days after AP chemotherapy and 8 days after gefitinib treatment, the patient suddenly developed a widespread eruption including acne-like rash on the face, erythema papules on the trunk and limbs, oral ulcer, and conjunctivitis ( and ), followed by a fever of 39°C. The rash gradually increased and aggravated, accompanied with blisters, pruritus, and ulceration. Twelve days after gefitinib treatment, the patient was hospitalized. Gefitinib was immediately stopped, and imipenem, amikacin, and fluconazole were administered intravenously as prophylaxis, and diphenhydramine and loratadine were given as an anti-allergy treatment. On the 13th day, the patient's condition deteriorated further with a fever of 42°C, fused mucocutaneous rash as well as diffuse vesicles and bullae ( and ), which coalesced and then sloughed, presenting a scalded appearance. A positive Nikolsky sign was present on her back and feet ( and ). After consulting dermatology doctors, the patient was diagnosed with TEN and transferred to the Dermatology Department at the Second Affiliated Hospital of Sun Yat-sen University for further treatment.\nRoutine laboratory testing showed a white blood cell (WBC) count of 6.26 × 109/L [reference value: (3.69-9.16) × 109/L], neutrophil (NEU) proportion of 73.1% (reference: 50%-70%), and C-reactive protein (CRP) level of 16.36 mg/L (reference: 0-8.2 mg/L); both the Mycoplasma pneumoniae IgM antibody and Mac strains were negative. No suspicious fungus was found in the oral swab examination, nor did bacteria grow in the skin secretion culture.\nImmunosuppressive treatment was started with 100 mg methylprednisolone (daily injection) for 9 days and intravenous immunoglobulin (20 g/day) for 5 days, followed by 10 g/day for 5 days, accompanied with imipenem and teicoplanin for anti-infection and other supportive treatment. This treatment led to a recurrence of the rash and the mucosal lesions, reepithelization of the denuded skin (), and improvement of the patient's general condition within 40 days. A chest computed tomography (CT) scan and brain magnetic resonance imaging (MRI) showed partial remission after treatment. The combination of AP and gefitinib was suspended; accordingly, the patient began treatment with icotinib (another EGFR-TKI made in China) after recovery, without exfoliative dermatitis or other similar toxicities. Stable disease was later achieved.
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.