key: cord-1024222-fxizweeq
authors: Godinho, Géssica Vasconcelos; Paz, Ana Luiza Lima Medeiros; de Araújo Gomes, Elâine Patrícia Alves; Garcia, Cristiane Loreda; Volpato, Luiz Evaristo Ricci
title: Extensive hard palate hyperpigmentation associated with chloroquine use
date: 2020-04-20
journal: Br J Clin Pharmacol
DOI: 10.1111/bcp.14313
sha: 4646f11f6f78679e8e265a1af5849848526c6ad4
doc_id: 1024222
cord_uid: fxizweeq

A 66‐year‐old woman diagnosed clinical manifestation of extensive hard palate hyperpigmentation is presented. Due to historic of rheumatoid arthritis and use of chloroquine phosphate for 3 years, exogenous hyperpigmentation associated with the drug was included among the possible diagnoses. Incisional biopsy was performed and the histopathological exam confirmed exogenous hyperpigmentation compatible with chloroquine use. The patient was referred to the rheumatologist and the ophthalmologist for evaluation of the continuity of the chloroquine use. After one year of follow‐up, no changes were seen in the hyperpigmentation nor other clinical changes. Hyperpigmentation of the hard palate by the use of chloroquine is one of the adverse effects of the chronic use of this drug and does not require specific treatment. The adequate anamnesis and the knowledge about the adverse effects of the drug allowed an adequate therapeutic approach in the case.

Pigmentary changes in the oral mucosa may be caused by many medications, including antimalarial drugs (chloroquine phosphate, hydroxychloroquine, quinidine and quinacrine), tranquilizers (chlorpromazine), chemotherapeutic drugs (doxorubicin, busulfan and cyclophosphamide), antiretroviral agents (AZT and ketoconazole), antibiotics (minocycline) and laxatives (phenolphthalein). 1 The pathogenesis underlying drug pigmentation can be categorized as arising from the deposition of metabolites or drugs in the dermis and epidermis, melanin deposition with or without melanocyte augmentation and drug-induced post-inflammatory mucosal changes. 2 Chloroquine phosphate, classified as an antimalarial agent due to its immunosuppressive potential and anti-inflammatory action, is also used for the treatment systemic lupus erythematosus and rheumatoid arthritis, in addition to other dermatological conditions. 1 Recent studies have brought attention to its possible benefit also in the treatment of patients infected by the novel emerged Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), 3-5 a pandemic that first broke out in China and spread rapidly worldwide. [4] [5] [6] In so doing, the use of chloroquine phosphate is expected to increase considerably, therefore, it is important to recognize its possible side effects.

In this paper, the case of a 66-year-old woman diagnosed with rheumatoid arthritis and using chloroquine phosphate for 3 years, with clinical manifestation of extensive hard palate hyperpigmentation is presented. In typical cases or with incomplete history, a biopsy is performed to aid the diagnosis. In atypical cases, biopsy is crucial to rule out melanoma. 12 Given the long-term history of chloroquine, the main diagnostic hypothesis was drug-induced endogenous oral hyperpigmentation. Differential diagnoses are cited as melanocytic nevus, amalgam tattooing, Addison's disease, vitamin B12 deficiency and melanoma. 8 Microscopically, hyperpigmentation of the oral mucosa of medicinal origin is characterized by an abnormal number of melanocytes in the epithelium and the presence of pigment granules within the lamina propria, between collagen fibers and within macrophages. When there are granules in the reticular lamina propria and lack of melanin deposition in the basal cell layer, it is pointed to the hyperpigmentation due to the use of hydroxychloroquine. 13 An incisional biopsy was performed and submitted to histopathological examination, whose report described the presence of blackened exogenous pigments in the lamina propria and subepithelial region, sometimes phagocytized by macrophages, as well as overlying epithelium with normal appearance. These characteristics are found in other cases described previously, confirm the diagnosis of druginduced oral pigmentation and rule out the hypothesis of neoplastic development. 1, 14 There is no need for treatment in these cases, and the possibility of reducing or stopping medication can be evaluated by the rheumatologist. It is also important to refer the patient for ophthalmologist F I G U R E 1 Clinical aspect of the color alteration present in the hard palate with a diameter of approximately 3 cm and evolution of 1 year F I G U R E 2 A, Histological sections showing fragment of oral mucosa coated with parakeratinized stratified paved epithelium. B, Exogenous pigmentation of blackish color arranged in bands evaluation due to the potential for chloroquine retinotoxicity. 15 The therapeutic approach adopted in this case report was to refer the patient to the ophthalmologist, as well as to keep her in periodic dental and rheumatological clinical follow-up.

Professionals shall jointly assess the risks and benefits of maintaining or stopping medication. As the use of chloroquine phosphate is probable to increase, it is important that clinicians know this uncommon side effect.

Hyperpigmentation of the hard palate by the use of chloroquine is one of the adverse effects of the chronic use of this drug and does not require specific treatment. The adequate anamnesis, the dentist's knowledge about the adverse effects of the drug and the establishment of differential diagnoses allowed an adequate therapeutic approach in the case presented and the referral to other medical areas for multidisciplinary approach.

There are no competing interests to declare. 

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