Antimalarials in the management of discoid and systemic lupus erythematosus☆

Hydroxychloroquine is widely used for the treatment of cutaneous lupus erythematosus (CLE). Although new recommendations exist for hydroxychloroquine dosing, there is still uncertainty about the dosage that will elicit a satisfactory response in CLE while limiting adverse effects, specifically retinopathy.

To summarize hydroxychloroquine dosages, outcomes, and adverse effects in the treatment of CLE, focusing on retinopathy.

A comprehensive literature search from inception to December 2018 was performed in Ovid MEDLINE, Ovid Embase, and The Cochrane Library (Wiley). Studies were screened against predefined inclusion and exclusion criteria.

Twelve studies were selected and included 5 retrospective studies, 3 prospective studies, 2 case series, and 2 randomized controlled trials. These studies show that a hydroxychloroquine dosage up to 400 mg/d is effective for most CLE patients (range of effectiveness, 50%-97%), with few adverse effects. One incidence of retinopathy, after a very high cumulative dose, was reported across all 12 studies (852 total patients).

Because retinopathy and other serious adverse effects may not appear until much later, many of these studies are limited by short follow-up time.

This evidence suggests that hydroxychloroquine for CLE is effective at 400 mg/d, with an exceedingly low incidence of retinopathy and other adverse effects.

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.

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.

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.

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.

The rapidly spreading Coronavirus Disease (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus (SARS-CoV-2), represents an unprecedented serious challenge to the global public health community. The extremely rapid international spread of the disease with significant morbidity and mortality made finding possible therapeutic interventions a global priority. While approved specific antiviral drugs against SARS-CoV-2 are still lacking, a large number of existing drugs are being explored as a possible treatment for COVID-19 infected patients. Recent publications have re-examined the use of Chloroquine (CQ) and/or Hydroxychloroquine (HCQ) as a potential therapeutic option for these patients. In an attempt to explore the evidence that supports their use in COVID-19 patients, we comprehensively reviewed the previous studies which used CQ or HCQ as an antiviral treatment. Both CQ and HCQ demonstrated promising in vitro results, however, such data have not yet been translated into meaningful in vivo studies. While few clinical trials have suggested some beneficial effects of CQ and HCQ in COVID-19 patients, most of the reported data are still preliminary. Given the current uncertainty, it is worth being mindful of the potential risks and strictly rationalise the use of these drugs in COVID-19 patients until further high quality randomized clinical trials are available to clarify their role in the treatment or prevention of COVID-19.