Reconsidering Antimalarials in Systemic Lupus Erythematosus: Developments of Translational Clinical Interest

Abstract

Successful trials of biologic therapies in systemic lupus erythematosus (SLE) have raised interest in targeting a variety of additional putative mechanisms of action. These include preparations that antagonize Toll-like receptors (TLR) 7 and 9, one of the actions of antimalarials. Although they have been studied for over a hundred years, the last decade has witnessed a flurry of reports demonstrating novel physiologic effects of these agents. Prospective and retrospective studies that document disease-modifying outcomes of antimalarials have appeared. This report summarizes those breakthroughs and insights, which are important in our approach toward SLE management. ### Historical context According to legend, bark from a “fever tree” in 1620s Peru miraculously cured the mysterious illness of the Countess of Cinchona. That event led the Jesuits in Europe to form the first modern cartel — one that controlled the international production and distribution of quinine by the 1660s1. The first modern clinical investigations of quinine for rheumatic disorders were not published until Payne’s report of its efficacy for cutaneous lupus in 18942 and were expanded upon in the 1920s and 1930s. The quinacrine story is among the most colorful in the annals of pharmacologic interventions. It was the last discovery by German bacteriologist Paul Ehrlich before he died in 1915. In the United States, President Franklin D. Roosevelt’s administration and congressional leadership had to go to court to get pro-German sympathizers at the Winthrop Chemical Company to disclose the quinacrine manufacturing process. … Address correspondence to Dr. Venuturupalli; E-mail: swamy.venuturupalli{at}gmail.com