How common is oral pigmentation with hydroxychloroquine?

Oral Pigmentation in the Hard Palate is a Potential Site of Hydroxychloroquine Pigmentation

Chloroquine and hydroxychloroquine are medications used to treat a variety of autoimmune diseases. In the hair loss world, we use these medications to treat lichen planopilaris, frontal fibrosing alopecia, discoid lupus, systemic lupus, and sometimes dermatomyositis (and other conditions too).

Chloroquine and hydroxychloroquine bind melanin pigment and this contributes to some of the pigment related side effects including accumulation in the retina (and eye damage) and accumulation in the skin (skin hyperpigmentation). The pigment can also accumulate in the gums and hard palate. Overall, hydroxychloroquine is considered be less toxic than chloroquine, owing to a lower tissue accumulation in melanin rich areas.

Silva et al, 2022

A new report by Silva and colleagues set out to evaluate the occurrence of oral pigmentation induced by chloroquine or hydroxychloroquine and to understand the pathogenic mechanism behind this phenomenon.

The authors evaluated 19 eligible studies. Sixteen studies were case reports, 2 had case–control design and 1 was cross-sectional. 44 cases of oral pigmentation were reported in the studies. The hard palate was the anatomic region most affected by hyperpigmentation (65.9%), followed by the buccal mucosa (22.7%). According to the case reports, most of the lesions (44%) were bluish-gray color. The minimum time from the beginning of treatment 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.

Conclusions

Pigmentation issues from hydroxychloroquine or chloroquine are really not all that rare. It has been estimated that the risk of pigmentation related side effects with hydroxychloroquine and chloroquine is 7-10%. The skin and mucosa can be affected. Although the mechanisms are not clear, some studies have suggested that trauma or injury to an area increases the chance that it will show pigmentation type issues with use of these drugs. Some studies have suggested that use of anticoagulants and oral steroids can also increase the risk.

One of the key differences between pigmentation in the skin and mucosa from the eye retinopathy side effects is that the risk of pigmentation in the mouth and skin does not depend so much on cumulative dose (as in the case of retinopathy). Most cases of pigmentation in the mouth or skin occur in the first 5 years.

The study reminds us that mucosal pigmentation can occur with these drugs. For the mouth, this study indicates that the hard palate is the most likely involved. The hyperpigmentation depends on drug dosage and treatment length. Hyperpigmentation was generally detected after a long period of treatment with chloroquine or hydroxychloroquine.

Other studies have shown that the anatomical regions with the buccal mucosa, labial mucosa and tongue are also sites of involvement.

This study examined specifically the mouth. I point out to readers that it’s important to remember that the skin can be involved too and the face, arms and shins can show the pigment side effect in around 10 % of users.

This study did not seek to understand the resolution of the pigment. most studies suggest that this is a permanent side effect although some partial improvement can occur either with stopping or with Q switched ruby laser for skin pigmentation. Treatment for the mouth is not clear but in and of itself is not a sign of toxicity and does not necessarily mandate stopping the drug.

REFERENCE

Silva PUJ et al. Oral pigmentation as an adverse effect of chloroquine and hydroxychloroquine use: A scoping review. Medicine (Baltimore).. 2022 Mar 18;101(11):e29044.

ADDITIONAL REFERENCES

Horta-Baas G. Chloroquine-induced oral mucosal hyperpigmentation and nail dyschromia. Hiperpigmentación de la mucosa oral y discromía ungueal inducida por cloroquina. Reumatol Clin 2018;14:177–8.

Chacón-Dulcey V et al. Oral manifestations associated with antimalarial therapy in patients with systemic lupus erythematosus. Lupus 2020;29:761–6.

Jallouli M et al. Hydroxychloroquine-induced pigmentation in patients with systemic lupus erythematosus: a case- control study. JAMA 2013;149:935–40.