The effect of increasing the dose of hydroxychloroquine (HCQ) in patients with refractory cutaneous lupus erythematosus (CLE): An open-label prospective pilot study

J Am Acad Dermatol. 2016 Apr;74(4):693-9.e3. doi: 10.1016/j.jaad.2015.09.064. Epub 2016 Feb 3.


Background: Up to 30% of patients with cutaneous lupus erythematosus (CLE) fail to respond to hydroxychloroquine (HCQ).

Objectives: We sought to evaluate the efficacy of increased daily doses of HCQ on cutaneous response in refractory CLE.

Methods: We conducted an open-label prospective study between 2010 and 2014. Patients with CLE and HCQ blood level less than or equal to 750 ng/mL were included. The daily dose of HCQ was increased to reach blood concentrations greater than 750 ng/mL. The primary end point was the number of responders defined by an improvement of CLE Disease Area and Severity Index score (4 points or 20% decrease) in patients with HCQ blood concentration greater than 750 ng/mL.

Results: We included 34 patients (26 women; median age 45 [range 28-72] years). Two nonadherent patients were excluded. The median CLE Disease Area and Severity Index score before treatment was significantly improved after treatment (8 [range 2-30] vs 1.5 [range 0-30]), P < .001). The primary response criterion was reached in 26 (81%) of the 32 patients analyzed. A decrease in HCQ doses without further CLE flare (median follow-up 15.8 [range 3.06-77.4] months) was achieved in 15 of the 26 responders.

Limitations: The main limitations of the study are its open-label design and the limited number of patients included.

Conclusions: Increasing HCQ doses to reach blood concentrations greater than 750 ng/mL should be considered before addition of other treatments in refractory CLE.

Keywords: antimalarials; cutaneous lupus erythematosus; hydroxychloroquine; hydroxychloroquine blood concentration; increasing dose; retinal toxicity.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Aged
  • Antimalarials / administration & dosage*
  • Antimalarials / adverse effects
  • Antimalarials / blood*
  • Chronic Disease
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Female
  • Follow-Up Studies
  • Humans
  • Hydroxychloroquine / administration & dosage*
  • Hydroxychloroquine / adverse effects
  • Hydroxychloroquine / blood*
  • Lupus Erythematosus, Cutaneous / diagnosis
  • Lupus Erythematosus, Cutaneous / drug therapy*
  • Male
  • Maximum Tolerated Dose
  • Middle Aged
  • Pilot Projects
  • Prospective Studies
  • Risk Assessment
  • Severity of Illness Index
  • Time Factors
  • Treatment Outcome


  • Antimalarials
  • Hydroxychloroquine