Oral pigmentation as an adverse effect of chloroquine and hydroxychloroquine use: A scoping review

BACKGROUND: Chloroquine and hydroxychloroquine are 2 medications used to treat some systemic diseases. OBJECTIVE: The aim of this scoping review was to assess the occurrence of oral pigmentation induced by chloroquine or hydroxychloroquine and to understand the pathogenic mechanism behind this phenomenon. METHODS: The review was performed according to the list of PRISMA SrC recommendations and the JBI Manual for Evidence Synthesis for Scoping Reviews. MEDLINE (PubMed), Scopus, EMBASE, SciELO, Web of Science, Lilacs, and LIVIVO were primary sources, and “gray literature” was searched in OpenThesis and Open Access Thesis and Dissertations (OATD). Studies that screened the occurrence of oral pigmentation associated to the use of chloroquine or hydroxychloroquine were considered eligible. No restrictions of year and language of publication were applied. Study selection and data extraction were performed by 2 independent reviewers. The risk of bias was assessed through the JBI tool, depending on the design of the selected studies. RESULTS: The initial search resulted in 2238 studies, of which 19 were eligible. Sixteen studies were case reports, 2 had case-control design and 1 was cross-sectional. Throughout the studies, 44 cases of oral pigmentation were reported. The hard palate was the anatomic region most affected with pigmentation (66%). According to the case reports, most of the lesions (44%) were bluish-gray. The minimum time from the beginning of treatment (chloroquine or hydroxychloroquine) to the occurrence of pigmentation was 6 months. The mean treatment time with the medications was 4.9 years, and the mean drug dosage was 244 mg. Most of the studies (63.1%) had low risk of bias (high methodological quality). CONCLUSIONS: The outcomes of this study suggest that hyperpigmentation depend on drug dosage and treatment length. Hyperpigmentation was detected after a long period of treatment with chloroquine or hydroxychloroquine.