Multifaceted effects of hydroxychloroquine in human disease

Objectives: Hydroxychloroquine (HCQ) is a widely used medication for the treatment of rheumatoid arthritis and systemic lupus erythematosus. An increasing body of evidence supports actions of this drug that are not directly related to its immunosuppressive or anti-rheumatic properties. The objective of this systematic review is to characterize the spectrum of conditions that might be responsive to treatment with HCQ. Methods: PubMed was searched using the MeSH for HCQ with relevant subheadings and the limits of human topics and English language. Four-hundred and fifty-six abstracts from this search were examined individually to exclude those that were not focused on the objectives of this review. The resulting 76 articles were grouped according to topic areas and reviewed in detail. Results: HCQ has been reported to have therapeutic effects in a wide array of conditions, including diabetes mellitus, dyslipidemias, coagulopathies, infectious diseases and malignancies. Mechanisms of action responsible for these effects likely include altered signaling through cellular receptors, post-glycosylation modifications of infectious agents, changes in levels of inflammatory mediators and inhibition of autophagy. Many of the pathways are likely dependent on drug-induced changes in intra-endosomal acidity. Conclusions: The use of, and interest in, HCQ has spread into many areas of medicine. Actions of this drug may be directly beneficial to patients with non-rheumatic conditions such as diabetes mellitus or viral infections. Further understanding of underlying mechanisms has potential to reveal modifiable pathogenic pathways that might elucidate approaches to the design of more effective therapeutics for many chronic diseases.