Epidermal growth factor receptor inhibitor related cutaneous toxicity
Introduction: Cutaneous toxicity is the second most commonly reported adverse event in the use of afatinib. Severe skin rashes in relation to afatinib can mimic cutaneous vasculitis due to other systemic-disorders. We present a case of 58-year-old man presenting with a vasculitic skin rash; where an oncologist review guided us towards the correct diagnosis and management but also enlightened us about a very unique feature about afatinib related skin-rashes.
Case: A 58-year-old Caucasian man attended the emergency department with sub-acute onset widespread skin rash with a productive cough and dyspnoea for a week. He denied any other systemic symptoms. He had a known diagnosis of non-small-cell lung cancer and was taking a biologic-agent whose name he couldn’t remember. He was not known to have any drug allergies, no other significant past medical or personal history and wasn’t taking any other medications.
He had a maculopapular skin rash with pustules and erythema around the lesions with few purpuric lesions over face, forehead, neck, trunk and limbs. There was palmo-plantar involvement but absent mucocutaneous, hair or nail involvement and he reported the rash to be extremely pruritic. Respiratory examination revealed bi-basal crepitations and rest of the systemic examination was unremarkable. In view of neutrophilic-leucocytosis and a consolidation on chest-radiograph patient was treated empirically for chest infection. There were no clinical or serological (auto-immune-profile) evidence of associated systemic disorder or atypical pneumonia.
An oncologist reviewed the patient on our request and at the bedside he spontaneously spotted this rash to be classical severe cutaneous toxicity secondary to patient’s current biologic therapy. Oncologist enlightened us that this patient was on Afatinib; which is a second-generation epidermal growth factor receptor (EGFR) inhibitor biologic approved for use in non-small-cell lung cancers (NSCLC) that are positive for EFGR-mutations. Interestingly, there is a direct relationship between this cutaneous toxicity and tumour response to these biologic-therapies; patients who experience more severe cutaneous-lesions have a greater response to this anti-neoplastic biologic-therapy.
After temporarily discontinuing the afatinib, he was started on oral dexamethasone for 7 days with chlorpheniramine with topical steroid cream and ointment with significant improvement in both skin symptoms and the lesions including pruritus at one-week follow-up.
Discussion: Our case-report highlighted that the patients on afatinib may develop numerous cutaneous adverse events including pruritus, papulopustular/maculopapular eruptions, vasculitis-mimicking rashes with leucocytoclastic-vasculitis on cutaneous biopsy. These skin rashes are generally manageable with appropriate treatment pause, supportive care and steroids. It also enlightened us about the fact that afatinib-induced cutaneous toxicity has a positive correlation with tumour response to this biologic-therapy.
