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

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-alpha) is very important. Therefore, treatment with an anti-TNF-alpha 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 degrees 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-alpha stimulated inflammation and also p53-related apoptosis occurs in AGEP, a TNF-alpha blocking agent such as etanercept may be effective for quick treatment.