Drug-induced lupus erythematosus: an update on drugs and mechanisms

Abstract

Purpose of review: Rapid introduction of newly developed drugs in the absence of clear understanding of the pathophysiologic mechanisms behind drug-induced lupus erythematosus (DILE) can sometimes make DILE difficult to recognize in clinical practice. The purpose of this review is to summarize drugs most recently reported to be involved in DILE and discuss the current landscape of diverse mechanisms involved.

Recent findings: A large number of proton pump inhibitor (PPI)-induced subacute cutaneous lupus erythematosus cases have been reported, suggesting a shift over time in the spectrum of drugs implicated in DILE. Twenty-two articles comprising 29 DILE case reports published within the last 2 years are summarized in this review, including 12 (41.4%) systemic DILE. Antitumor necrosis factor (anti-TNF) drugs were the most frequently (41.7%) reported to introduce systemic DILE in these cases. Chemotherapeutic drugs were the most common drug class (54.5%) involved in subacute cutaneous lupus erythematosus, with an observed higher incidence in female patients. Enhanced neutrophil extracellular trap (NET) formation induced by procainamide and hydralazine could be a new mechanism contributing to the pathogenesis of DILE.

Summary: The list of drugs implicated in triggering DILE is expanding as new drugs with novel mechanisms of action are being developed. It is important to recognize culprit drugs that may induce lupus erythematosus, as discontinuation usually results in improvement of drug-induced manifestations. Characterizing the mechanisms involved might help better understand the cause of idiopathic autoimmunity.

FIGURE 1.

Mechanisms involved in the pathogenesis of drug-induced lupus erythematosus. Genetic predisposition, drug biotransformation and epigenetic dysregulation are three important components of current proposed pathogenic mechanisms of DILE. Instead of working independently, these factors are likely to interact with each other to cause DILE. Genetic predisposition: Studies revealing genetic predisposition could be summarized in three main aspects, listed in the left upper circle. Biotransformation: Procainamide undergoes neutrophil-mediated oxidative metabolism to produce procainamide hydroxylamine (PAHA). PAHA, myeloperoxidase (MPO), and reactive oxygen species contribute to direct cytotoxicity. Epigenetic dysregulation: Drugs and some drug metabolites exert epigenetic dysregulation on T cells and B cells (1,2), macrophages (3) and neutrophils (4), which eventually leads to autoreactive T cell and B cell generation, triggering DILE.