Rapid onset of cutaneous squamous cell carcinoma in patients with rheumatoid arthritis after starting tumor necrosis factor alpha receptor IgG1-Fc fusion complex therapy.

Tumor necrosis factor alpha (TNF-alpha) is now believed to be a major contributor to the pathogenesis of the synovitis and joint destruction in rheumatoid arthritis. Etanercept is a recombinant human TNF-alpha receptor Fc fusion protein consisting of a dimer of the extracellular portion of two p75 TNF-alpha receptors fused to the Fc portion of human IgG1. Etanercept produces significant dose-dependent improvements in disease activity. We describe 7 patients who experienced 1 or more squamous cell carcinomas that showed rapid growth and arose over a 2- to 4-month period of etanercept therapy. Soluble TNF-alpha receptor therapy through inhibition of a T(H)1 cytokine pattern and inhibition of the direct and indirect cytotoxic effects of TNF-alpha may initially decrease mechanisms for controlling subclinical tumors and may contribute to the histologic features seen within these tumors. However, prolonged TNF-alpha inhibition may have some antitumor effects.