Simple dose-escalation regimen for hydroxychloroquine-induced hypersensitivity reaction in patients with systemic lupus erythematosus enabled treatment resumption

Lupus. 2019 Oct;28(12):1473-1476. doi: 10.1177/0961203319879987. Epub 2019 Oct 1.

Abstract

Objective: This study aimed to investigate the risk factors of hydroxychloroquine (HCQ)-induced hypersensitivity in patients with systemic lupus erythematosus (SLE) and to propose a simple dose-escalation regimen in cases of mild HCQ-induced hypersensitivity.

Methods: We identified patients with SLE who started HCQ between 2009 and 2018 and cases of HCQ-induced hypersensitivity by reviewing the electronic medical charts. A simple dose-escalation regimen, starting at 40 mg/day with weekly increments of 40 mg/day to 200 mg/day, was used in patients with HCQ-induced hypersensitivity who did not require hospitalization or systemic steroid therapy. We then compared the clinical parameters of patients with and without HCQ-induced hypersensitivity and evaluated the success of our dose-escalation regimen.

Results: We enrolled 302 patients with SLE and identified 25 cases of HCQ-induced eruption (8.3%). The mean Naranjo score of these patients was 5.1 ± 1.4 (min 3, max 8), and all 25 patients received a 'possible' (9) or 'probable' (16) score. A mild, generalized, maculopapular rash occurred in 24 patients, and urticaria occurred in one patient at 24 days (interquartile range 15-40 days) after the start of treatment. The proportion of cyclophosphamide use, glucocorticoid consisting of prednisolone 20 mg/day or more, and initiation of SMX-TMP within 28 days were higher in patients with skin eruptions. On multivariate analysis, only cyclophosphamide use was identified as a risk factor of HCQ-induced hypersensitivity (odds ratio = 12.3 (95% confidential interval 1.4-14.3)). Thirteen of the 14 patients on the dose-escalation regimen (92.9%) tolerated continued HCQ treatment. One patient re-experienced eruptions on day 10 day after starting HCQ.

Conclusions: Mild late reactions are common in HCQ-induced hypersensitivity. A simpler dose-escalation regimen enables safe and easier reintroduction of HCQ but should not be applied to patients with immediate reactions or moderate late reactions.

Keywords: Systemic lupus erythematosus; desensitization; hydroxychloroquine; hypersensitivity reaction; simple dose-escalation regimen.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / therapeutic use
  • Antirheumatic Agents / administration & dosage*
  • Antirheumatic Agents / adverse effects
  • Antirheumatic Agents / therapeutic use
  • Clinical Protocols
  • Cyclophosphamide / adverse effects
  • Dose-Response Relationship, Drug
  • Drug Hypersensitivity / drug therapy*
  • Drug Therapy, Combination
  • Female
  • Glucocorticoids / administration & dosage
  • Glucocorticoids / therapeutic use
  • Humans
  • Hydroxychloroquine / administration & dosage*
  • Hydroxychloroquine / adverse effects
  • Hydroxychloroquine / therapeutic use
  • Immunosuppressive Agents / adverse effects
  • Japan / epidemiology
  • Lupus Erythematosus, Systemic / drug therapy*
  • Male
  • Middle Aged
  • Prednisolone / administration & dosage
  • Prednisolone / therapeutic use
  • Retrospective Studies
  • Risk Factors
  • Trimethoprim, Sulfamethoxazole Drug Combination / administration & dosage
  • Trimethoprim, Sulfamethoxazole Drug Combination / therapeutic use

Substances

  • Anti-Bacterial Agents
  • Antirheumatic Agents
  • Glucocorticoids
  • Immunosuppressive Agents
  • Hydroxychloroquine
  • Trimethoprim, Sulfamethoxazole Drug Combination
  • Cyclophosphamide
  • Prednisolone