The molecular mechanism of etanercept, an anti-tumour necrosis factor-a receptor-fusion protein, in the treatment of acute generalized exanthematous pustulosis

Abstract

Introduction: Acute generalized exanthematous pustulosis (AGEP) is one of the severe adverse cutaneous drug reactions. In its pathophysiology, releasing of tumour necrosis factor-alpha (TNF-α) is very important. Therefore, treatment with an anti-TNF-α receptor-fusion protein, such as etanercept, may be effective. Objective: To present a case and evaluate the molecular mechanism of etanercept in the treatment of AGEP. Case: A 53-year-old woman with multiple disseminated pustules and a rash on the upper part of her back, which was progressively worsening and spreading to approximately 60–70% of the skin on her back, and fever (38.7°C), was admitted to our department. After etanercept treatment, all the symptoms were rapidly improved and the patient's skin practically cleared within 5 days. Biopsy samples taken from this patient with AGEP before and after etanercept treatment were stained immunohistochemically with p53 and bcl-2 antibodies and also an apoptosis detection kit. Results: In epidermis, increasing p53 expression-related apoptosis and decreasing bcl-2 expression was detected. However, after etanercept treatment, p53 expression-related apoptosis decreased and bcl-2 expression increased. Conclusion: Because TNF-α stimulated inflammation and also p53-related apoptosis occurs in AGEP, a TNF-α blocking agent such as etanercept may be effective for quick treatment.

• AGEP
• apoptosis
• bcl-2
• etanercept
• p53
• TNF-α