Skip to main content
SpringerLink
Log in

Hydroxychloroquine-Induced Retinopathy

A Dermatologic Perspective

  • Review Article
  • Published:
American Journal of Clinical Dermatology Aims and scope Submit manuscript

Abstract

Dermatologists use antimalarials to treat conditions such as cutaneous lupus erythematosus. One potentially serious adverse effect of these agents is irreversible maculopathy. Although there is some evidence that hydroxychloroquine and chloroquine have similarly narrow therapeutic indices with regard to retinal toxicity, the former is thought to be less damaging to the retina and is thus more widely employed by dermatologists. The current recommended maximal dose for hydroxychloroquine is 6.5 mg/kg/day, with the weight in kilograms used for this calculation being the ideal bodyweight rather than actual bodyweight. Ophthalmologic follow-up is an important component of monitoring patients taking antimalarials. Recommendations for follow-up frequency have varied, and we present the recent guidelines from the American Academy of Ophthalmology. Despite dose limitations and ophthalmologic monitoring, irreversible retinal damage can occur. Among the reported cases, there does not seem to be any obvious predictor of the development of maculopathy. The idiosyncratic nature of this adverse effect may be related to interindividual differences in drug metabolism. To understand why only some patients develop retinopathy, better pharmacokinetic models need to be developed, and further elucidation of the precise mechanism of retinal damage is required.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Table I
Table II

Similar content being viewed by others

References

  1. Millard T, Hughes G. Antimalarials. In: Wakelin SH, Maibach HI, editors. Handbook of systemic drug treatment in dermatology. London: Manson Publishing Ltd, 2004: 80–7

    Google Scholar 

  2. Rees RB, Maibach HI. Chloroquine: a review of reactions and dermatologic indications. Arch Dermatol. 1963 Sep; 88: 280–9

    Article  PubMed  CAS  Google Scholar 

  3. Callen JP, Camisa C. Antimalarial agents. In: Wolverton SE, editor. Comprehensive dermatologic drug therapy. Philadelphia (PA): WB Saunders Company, 2001: 251–68

    Google Scholar 

  4. Raines MF, Bhargava SK, Rosen ES. The blood-retinal barrier in chloroquine retinopathy. Invest Ophthalmol Vis Sci. 1989 Aug; 30 (8): 1726–31

    PubMed  CAS  Google Scholar 

  5. Mackenzie AH. Dose refinements in long-term therapy of rheumatoid arthritis with antimalarials. Am J Med. 1983 Jul; 75 (IA): 40–5

    Article  PubMed  CAS  Google Scholar 

  6. American College of Rheumatology Ad Hoc Committee on Clinical Guidelines. Guidelines for monitoring drug therapy in rheumatoid arthritis. Arthritis Rheum. 1996 May; 39 (5): 723–31

    Article  Google Scholar 

  7. Physicians’ desk reference. 58th ed. Montvale (NJ): Thomson PDR, 2004

  8. Marmor MF. New American Academy of Ophthalmology recommendations on screening for hydroxychloroquine retinopathy [letter]. Arthritis Rheum. 2003 Jun; 48 (6): 1764

    Article  PubMed  Google Scholar 

  9. Marmor MF, Carr RE, Easterbrook M, et al. Recommendations on screening for chloroquine and hydroxychloroquine retinopathy: a report by the American Academy of Ophthalmology. Ophthalmology. 2002 Jul; 109 (7): 1377–82

    Article  PubMed  Google Scholar 

  10. Katzung BG. Special aspects of geriatric pharmacology. In: Katzung BG, editor. Basic and clinical pharmacology. 9th ed. New York: McGraw Hill, 2004: 1007–14

    Google Scholar 

  11. Levy GD, Munz SJ, Paschal J, et al. Incidence of hydroxychloroquine retinopathy in 1207 patients in a large multicentre outpatient practice. Arthritis Rheum. 1997 Aug; 40 (8): 1482–6

    Article  PubMed  CAS  Google Scholar 

  12. Bernstein HN. Ocular safety of hydroxychloroquine. Ann Ophthalmol. 1991 Aug; 23 (8): 292–6

    PubMed  CAS  Google Scholar 

  13. Weiner A, Sandberg MA, Gaudio AR, et al. Hydroxychloroquine retinopathy. Am J Ophthalmol. 1991 Nov; 112 (5): 528–34

    PubMed  CAS  Google Scholar 

  14. Falcone PM, Paolini L, Lou PL. Hydroxychloroquine toxicity despite normal dose therapy. Ann Ophthalmol. 1993 Oct; 25 (10): 385–8

    PubMed  CAS  Google Scholar 

  15. Mavrikakis M, Papazoglou S, Sfikakis PP, et al. Retinal toxicity in long term hydroxychloroquine treatment. Ann Rheum Dis. 1996 Mar; 55 (3): 187–9

    Article  PubMed  CAS  Google Scholar 

  16. Bienfang D, Coblyn JS, Liang MH, et al. Hydroxychloroquine retinopathy despite regular ophthalmologic evaluation: a consecutive series. J Rheumatol. 2000 Nov; 27 (11): 2703–6

    PubMed  CAS  Google Scholar 

  17. Warner AE. Early hydroxychloroquine macular toxicity. Arthritis Rheum. 2001 Aug; 44 (8): 1959–61

    Article  PubMed  CAS  Google Scholar 

  18. Alarcon GS. How frequently and how soon should we screen our patients for the presence of antimalarial retinopathy?. [letter] Arthritis Rheum. 2002 Feb; 46 (2): 561

    Article  PubMed  Google Scholar 

  19. Easterbrook M. Dosage of hydroxychloroquine should be based on ideal body weight: comment on the letter by Alarcon. Arthritis Rheum. 2003 Mar; 48 (3): 863–4

    Article  PubMed  Google Scholar 

  20. Tell SE, Cutler DJ, Day RO, et al. Bioavailability of hydroxychloroquine tablets in healthy volunteers. Br J Clin Pharmacol. 1989 Jun; 27 (6): 771–9

    Article  Google Scholar 

  21. Furst DE, Lindsley H, Baethge B, et al. Dose-loading with hydroxychloroquine improves the rate of response in early, active rheumatoid arthritis: a randomized, double-blind six-week trial with eighteen-week extension. Arthritis Rheum. 1999 Feb; 42 (2): 357–65

    Article  PubMed  CAS  Google Scholar 

  22. Tell SE, Cutler DJ, Day RO, et al. A dose-ranging study of the pharmacokinetics of hydroxychloroquine following intravenous administration to healthy volunteers. Br J Clin Pharmacol. 1988 Sep; 26 (3): 303–13

    Article  Google Scholar 

  23. Tell SE, Cutler DJ, Brown KF. High-performance liquid chromatographic assay for hydroxychloroquine and metabolites in blood and plasma, using a stationary phase of poly(styrene divinylbenzene) and a mobile phase at pH 11, with fluorimetric detection. J Chromatogr. 1985 Nov; 344: 241–8

    Article  Google Scholar 

  24. Tell SE, Cutler DJ, Beck C, et al. Concentration-effect relationship of hydroxychloroquine in patients with rheumatoid arthritis: a prospective, dose ranging study. J Rheumatol. 2000 Jul; 27 (7): 1656–60

    Google Scholar 

  25. Munster T, Gibbs JP, Shen D, et al. Hydroxychloroquine concentration-esponse relationships in patients with rheumatoid arthritis. Arthritis Rheum. 2002 Jun; 46 (6): 1460–9

    Article  PubMed  CAS  Google Scholar 

  26. Carmichael SJ, Charles B, Tell SE. Population pharmacokinetics of hydroxychloroquine in patients with rheumatoid arthritis. Ther Drug Monit. 2003 Dec; 25 (6): 671–81

    Article  PubMed  CAS  Google Scholar 

  27. Shroyer NF, Lewis RA, Lupski JR. Analysis of the ABCR (ABCA4) gene in 4-aminoquinoline retinopathy: is retinal toxicity by chloroquine and hydroxychloroquine related to Stargardt disease?. Am J Ophthalmol. 2001 Jun; 131 (6): 761–6

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

There were no sources of funding and no conflicts of interest directly relevant to the contents of this manuscript.

Author information

Authors and Affiliations

  1. Department of Dermatology and Skin Sciences, University of British Columbia, Vancouver, Canada

    Jackie M. Tripp

  2. UCSF Department of Dermatology, University of California School of Medicine, 90 Medical Center Way, Box 0989, Surge 110, San Francisco, California, CA 94143-0989, USA

    Howard I. Maibach

Authors
  1. Jackie M. Tripp
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Howard I. Maibach
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tripp, J.M., Maibach, H.I. Hydroxychloroquine-Induced Retinopathy. Am J Clin Dermatol 7, 171–175 (2006). https://doi.org/10.2165/00128071-200607030-00003

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00128071-200607030-00003

Keywords

Search

Navigation