osimertinib and Stevens-Johnson-Syndrome

Toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS) are life-threatening dermatologic adverse events in the same category, caused by a delayed-type drug hypersensitivity reaction. Although skin toxicity is common during treatment with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), osimertinib-associated TEN is quite rare-thus far, only one report has been published from China. We report a case of an 80-year-old Japanese woman with lung adenocarcinoma harboring an EGFR-sensitizing mutation who was treated with osimertinib as the first-line treatment. Forty-six days after osimertinib induction, diffuse erythematous rash rapidly spread over the patient's trunk along with vesicles and purpuric macules; furthermore, she developed targetoid erythema on the face. Despite osimertinib discontinuation and corticosteroid treatment, diffuse erythema with Nikolsky's sign, general epidermal detachment, erosion and loose blisters developed over her entire body including the face. Based on her symptoms, TEN was diagnosed and thus, intravenous immunoglobulin was immediately administered for 4 days. The treatment ameliorated TEN-associated skin toxicity and caused epithelialization. Reports on osimertinib-associated SJS/TEN are scarce and only one report each on SJS and TEN from China is available. This is the first report of osimertinib-associated TEN from Japan. Cases of EGFR-TKI-associated SJS/TEN have been reported predominantly from Asian countries, suggesting ethnicity and genetic linkage play a role in the underlying mechanism.

Topics: Acrylamides; Adenocarcinoma; Aged, 80 and over; Aniline Compounds; Antineoplastic Agents; Asian People; ErbB Receptors; Female; Humans; Immunoglobulins, Intravenous; Lung Neoplasms; Mutation; Protein Kinase Inhibitors; Stevens-Johnson Syndrome

Topics: Acrylamides; Aniline Compounds; Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Drug-Related Side Effects and Adverse Reactions; ErbB Receptors; Exanthema; Female; Humans; Lung Neoplasms; Middle Aged; Mutation; Stevens-Johnson Syndrome; Tears; Ulcer

Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are a strain of small molecule inhibitors mainly used to treat the metastatic non-small cell lung cancer. Their predominant adverse effect is skin toxicity, usually manifested as acneiform rash, skin fissure, xerosis, and paronychia. Severe epidermal necrosis and exfoliation rarely occur. As one of the new generation of epidermal growth factor receptor-tyrosine kinase inhibitors, AZD-9291 is claimed to have better efficacy and fewer side effects, particularly appropriate for patients with EGFR T790M mutation. Herein we report a 51-year-old man who developed a large area of skin necrosis and was diagnosed with toxic epidermal necrolysis after AZD-9291 ingestion.

Topics: Acrylamides; Aniline Compounds; Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Dose-Response Relationship, Drug; ErbB Receptors; Humans; Lung Neoplasms; Male; Middle Aged; Protein Kinase Inhibitors; Stevens-Johnson Syndrome