Background Hydroxychloroquine (HCQ) has been used in the therapy of SLE for more than 50 years. The importance of this drug has been increasingly recognised within the last 10 years.

Methods A critical review of the literature as well as the author’s point of view will be offered.

Results Recent studies have confirmed the effects of HCQ in improving survival, decreasing SLE flares, reducing damage accrual and infections. In addition, beneficial effects in pregnant women include a reduction in preterm delivery and fetal growth restriction, as well as a reduction in the risk for cardiac neonatal lupus in babies born to anti-Ro-positive mothers. The addition of Mepacrine to therapy including HCQ has proven very effective in SLE patients with refractory skin and/or articular activity.

The risk for serious side effects is low even after prolonged use of the drug. Maculopathy is the most feared side effect of HCQ. The recent availability of sensitive screening techniques (particularly, the spectrum domain-optic coherence tomography, or SD-OCT) help capture cases of early (i.e. reversible) toxicity, but also increases the probability of discontinuation of the drug. Recent guidelines suggest that daily doses >5 mg/kg/d of HCQ are the main predictor of toxicity. Some authors have questioned this recommended reduction of the usual dose and the utility of blood levels of HCQ to predict retinal toxicity has also been proposed.

In the author’s experience, doses of 200 mg/d are sufficient for the majority of patients. Indeed, in our cohort studies showing protection of HCQ against thrombosis, infections, cancer and improved survival, most patients were treated with 200 mg/d, which reassures the efficacy of such doses.

Conclusions HCQ is the background therapy of SLE and should be recommended long-term in all patients without contraindications. Doses of 200 mg/d are effective and safe and should be considered the standard of care. The addition of Mepacrine potentiates the effects of HCQ in patients with non-responsive skin and/or articular activity. HCQ must not be stopped during pregnancy. Screening for retinal toxicity using sensitive techniques, including SD-OCT must be assured following recent recommendation. In addition, it is very important that a skilled and experience team of ophthalmologists, in close contact with lupus doctors, take care of the screening, in order to avoid unnecessary discontinuations of this essential drug.