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.
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.