Toxic epidermal necrolysis related to AP (pemetrexed plus cisplatin) and gefitinib combination therapy in a patient with metastatic non-small cell lung cancer

Toxic epidermal necrolysis (TEN) is a rare acute life-threatening mucocutaneous disorder that is mostly drug-related (80%–95%). It is clinically characterized as a widespread sloughing of the skin and mucosa. AP regimen (pemetrexed plus cisplatin) has been the preferred first-line chemotherapy for metastatic non-squamous non-small cell lung cancer (NSCLC). Gefitinib, a small-molecule epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), has already been recommended as a first-line treatment in EGFR-mutant metastatic NSCLC. We report rare presentation of TEN involving adverse effects of AP and gefitinib combination treatment in a 42-year-old woman diagnosed with metastatic NSCLC harboring an EGFR mutation. On the 21st day after administration of the first cycle of AP regimen and the 8th day after the initiation of gefitinib treatment, she developed an acne-like rash, oral ulcer, and conjunctivitis, which later became blisters and ultimately denuded. The characteristic clinical courses were decisive for the diagnosis of TEN. Treatment with systemic steroids and immunoglobulin as well as supportive treatment led to an improvement of her general condition and a remarkable recovery.

[1]  R. Schwartz,et al.  Toxic epidermal necrolysis: Part I. Introduction, history, classification, clinical features, systemic manifestations, etiology, and immunopathogenesis. , 2013, Journal of the American Academy of Dermatology.

[2]  R. Schwartz,et al.  Toxic epidermal necrolysis , 2020, Definitions.

[3]  M. Flaig,et al.  Toxic Epidermal Necrolysis after Pemetrexed and Cisplatin for Non-Small Cell Lung Cancer in a Patient with Sharp Syndrome , 2012, Oncology Research and Treatment.

[4]  C. Kahl,et al.  Toxic Epidermal Necrolysis Related to Cisplatin and Pemetrexed for Metastatic Non-Small Cell Lung Cancer , 2012, Oncology Research and Treatment.

[5]  O. Sokumbi,et al.  Clinical features, diagnosis, and treatment of erythema multiforme: a review for the practicing dermatologist , 2012, International journal of dermatology.

[6]  F. Kerdel,et al.  Painful generalized erythematous patches: a severe and unusual cutaneous reaction to pemetrexed. , 2011, Journal of the American Academy of Dermatology.

[7]  L. French,et al.  Toxic epidermal necrolysis and Stevens-Johnson syndrome , 2010, Orphanet journal of rare diseases.

[8]  J. Bosch-Barrera,et al.  Toxic Epidermal Necrolysis Related to Pemetrexed and Carboplatin with Vitamin B12 and Folic Acid Supplementation for Advanced Non-Small Cell Lung Cancer , 2009, Oncology Research and Treatment.

[9]  E. van Marck,et al.  Acute generalized exanthematous pustulosis after pemetrexed, and recurrence after re‐introduction , 2009, Clinical and experimental dermatology.

[10]  C. Gaudy-Marqueste,et al.  Toxicité cutanée grave après pemetrexed en traitement de deuxième ligne pour un cancer bronchique , 2007 .

[11]  D. Rosmarin,et al.  Toxic epidermal necrolysis. , 2007, Journal of the American Academy of Dermatology.

[12]  L. Raez,et al.  Pemetrexed-associated urticarial vasculitis. , 2006, Lung cancer.

[13]  L. Naldi,et al.  Risk of Stevens-Johnson syndrome and toxic epider mal necrolysis during first weeks of antiepileptic therapy: a case-control study , 1999, The Lancet.

[14]  C. Hook,et al.  Severe exfoliative dermatitis associated with hand ischemia during cisplatin therapy. , 1994, Mayo Clinic proceedings.

[15]  D. Goldenberg,et al.  Stevens‐Johnson Syndrome, Respiratory Distress and Acute Renal Failure Due to Synergic Bleomycin‐Cisplatin Toxicity , 1989, Journal of clinical pharmacology.