Hydroxychloroquine Induced Hyperpigmentation of Buccal Mucosa in a Pediatric Patient

Introduction

The incidence of cutaneous hyperpigmentation with the antimalarials like hydroxychloroquine and chloroquine has been reported to run as high as 10% to 25%.^1,2 Till now sixteen cases of pigmentation due to HCQ have been reported.^3-17 Thus hydroxychloroquine-induced hyperpigmentation is not a rare adverse effect. But only one literature review is focused on buccal mucosa hyperpigmentation¹⁰ and no cases were reported in pediatric population. In this case, the adverse reaction is caused to an 8 year old patient with four days of the drug exposure.

Case report

A 8 year old female child who was a known case of SLE was on tab. Hydroxychloroquine, stopped all the medications three months back. Later she presented with fever, intermittent type that increased at night associated with breathlessness and cough, admitted to the hospital. History revealed that she was diagnosed with hyper IgE syndrome post disseminated tuberculosis, completed her Anti Tubercural Therapy (ATT). After few months of ATT completion she was diagnosed with SLE and was on hydroxychloroquine for one month. Later she discontinued the drug and the parents consulted other prescriber and where she was prescribed with tab. Rifampin for one month. Now on hospital admission she started with antimicrobials like inj.amoxicillin clavulanic acid, syrup azithromycin and nebulizations for upper respiratory tract infections. After 4 days of hospital admission the patient presented multiple erythematous papules and plaques on face and left hand and diagnosed as exanthematous rash. She was advised with fusidic acid cream, hydroxyzine hydrochloride syrup and atogla lotion constituting borage oil, aloe vera gel and wheat germ oil. Along with this, started with tablet Hydroxychloroquine 100mg/day for SLE. After 4 days of prescription with hydroxychloroquine started the severe bluish grey discoloration of buccal mucosa involving gums and lips (Figure 1). The bluish grey hyperpigmentation was confirmed due to the prescription of hydroxychloroquine. The discoloration did not spread to other areas of the mouth. Therapy was continued with no change in the coloration or other drug induced symptoms on hospital admission.

Hydroxychloroquine induced hyperpigmentation of buccal mucosa ADR were assessed for causality according WHO-UMC Causality Categories and it was found certain, severity assessed by Hartwig and Siegel severity scale and found moderate and whereas probability by Naranjo algorithm ADR probability scale, the score was found 5 indicate probable ADR.

Discussion

Use of antimalarials (ie, Quinacrine, Chloroquine, Hydroxychloroquine [HCQ]) can induce tissue pigmentation in a variety of organs, including skin, joint tissue, trachea, and cartilage in the nose and ears.^1,2 To our knowledge 16 cases were reported^1,3-17 on hyperpigmentation induced due to hydroxychloroquine and only one case is on buccal mucosa and this presents on hard palate.¹⁰ On a search of similar adverse reaction caused by chloroquine diphosphate on hard palate showed seven case reports.

The lesions of hydroxychloroquine-induced hyperpigmentation are typically blue-grey macules that enlarge and become confluentover the affected body parts. The distribution of hyperpigmentation varies widely.^1,3-17 The head, neck, trunk, upper extremities, and lower extremities are each reportedly involved in roughly one-half of the cases. Thehyperpigmentation begins in most patients after about four months of treatment with hydroxychloroquine. After discontinuation of the drug, there is a reduction in the level of hyperpigmentation, but it does not resolve completely.⁵

Here is a pediatric case with the previous exposure of hydroxychloroquine for one month after which there is a period of three months of nonadherence of the drug and further on reestablish the treatment with four days of hydroxychloroquine the child presented with the bluish grey discoloration of the buccal mucosa including the lips and gums. The pathophysiology of this process is unclear. There are dermal melanin deposits in biopsy specimens in few studies, but unlike a fixed drugeruption, these are not preceded by an inflammatory phase and damage to the junction of dermoepidermal.⁵ In vitro and in vivostudies have shown that antimalarial drugs can bind to melanin¹⁸, but the importance of this binding and its role in eye toxicityand skin hyperpigmentation has not been thoroughly investigated.

Conclusion

To conclude in this case bluish grey hyperpigmentation was confirmed due to the prescription of hydroxychloroquine in patient and recommended to have a close monitoring of children for development of hyperpigmentation of gums and lips whenever hydroxychloroquine is prescribed.

Acknowledgement

We are thankful to Principal and Head, Department of Clinical Pharmacy, H.S.K. College of Pharmacy and Principal and Dean, S N Medical College and HSK Hospital and Research centre, Bagalkot, Karnataka, India, for providing necessary facilities.

Conflict of interest

The authors have no conflicts of interest.