Article
Case Report

Mallappa Shalavadi1*, VM Chandrashekhar1 , Julia Jose2

1Department of Pharmacology, HSK College of Pharmacy, Bagalkot-587101, Karnataka, India.

2Pharmacy Assistant at Rexall Pharmacy Group Ltd., Scarborough, Ontario, Canada.

Corresponding author:

Dr. Mallappa Shalavadi, Department of Pharmacology, HSK College of Pharmacy, , Bagalkot-587101, Karnataka, India, Email: mallu.sha007@gmail.com 

Received Date: 18/06/2020 Accepted Date : 26/08/2020

Year: 2020, Volume: 10, Issue: 3, Page no. 30-32,
Views: 422, Downloads: 10
Licensing Information:
CC BY NC 4.0 ICON
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0.
Abstract

Hydroxychloroquine is a antimalarial drug and is one of the mainstay treatment of Systemic Lupus Erythematosus (SLE). The hyperpigmentation due to this drug is not a rare adverse effect. But the hyperpigmentation of buccal mucosa is reported only in one case. The drug has been rarely reported of such cases in the pediatrics with short term exposure. In this report we present case of an 8 year old child and she is known case of SLE was on hydroychloroquine for one month and discontinued the drug after that. Later after two months, on hospital admission started the drug, after 4 days drug administration to patient, the bluish discoloration of buccal mucosa including gum and lips was noticed. The discoloration did not spread to other areas of the mouth.

<p>Hydroxychloroquine is a antimalarial drug and is one of the mainstay treatment of Systemic Lupus Erythematosus (SLE). The hyperpigmentation due to this drug is not a rare adverse effect. But the hyperpigmentation of buccal mucosa is reported only in one case. The drug has been rarely reported of such cases in the pediatrics with short term exposure. In this report we present case of an 8 year old child and she is known case of SLE was on hydroychloroquine for one month and discontinued the drug after that. Later after two months, on hospital admission started the drug, after 4 days drug administration to patient, the bluish discoloration of buccal mucosa including gum and lips was noticed. The discoloration did not spread to other areas of the mouth.</p>
Keywords
Hydroxychloroquine, Hyperpigmentation, Systemic Lupus Erythematosus, Adverse Drug Reaction.
Downloads
  • 1
    FullTextPDF
Article

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 reported1,3-17 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.

 

Supporting Files
References

1. Puri PK, Lountzis NI, Tyler W, Ferringer T. Hydroxychloroquine-induced hyperpigmentation:the staining pattern. J Cutan Pathol. 2008;35:1134-37.

2. Hendrix JD Jr, Greer KE. Cutaneous hyperpigmentation caused by systemic drugs. Int J Dermatol. 1992;31:458-66.

3. Sawalha AH. Hydroxychloroquine-induced hyperpigmentation of the skin. J Rheumatol. 2015;42:135-6.

4. Kasper RS, Flueckiger B, Gobbi S, Lautenschlager S, Borelli S. Hydroxychloroquine-induced hyperpigmentation. J Dtsch Dermatol Ges. 2014;12:158-61.

5. Mir A, Boyd KP, Meehan SA, McLellan B. Hydroxycholoroquine-induced hyperpigmentation. Dermatol Online J. 2013;19:20723.

6. Cohen PR. Hydroxychloroquine associated hyperpigmentation mimicking elder abuse. Dermatol Ther (Heidelb). 2013;3:203-10.

7. Tracy CL, Blakey B, Parker G, Roebuck J. Hydroxychloroquine-induced hyperpigmentation. J Clin Rheumatol. 2013;19:292.

8. Jallouli M, Francès C, Piette JC, Huong du LT, Moguelet P, Factor C et al. Hydroxychloroquine-induced pigmentation in patients with systemic lupus erythematosus: a case-control study. JAMA Dermatol. 2013;149:935-40.

9. Sifuentes Giraldo WA, Grandal Platero M, de la Puente Bujidos C, Gámir Gámir ML. Generalized skin hyperpigmentation and longitudinal melanonychia secondary to treatment with hydroxychloroquine in systemic lupus erythematosus. Reumatol Clin. 2013;9:381-2.

10. Kalampalikis A, Goetze S, Elsner P. Isolated hyperpigmentation of the oral mucosa due to hydroxychloroquine. J Dtsch Dermatol Ges. 2012;10:921-2.

11. Cho EB, Kim BC, Park EJ, Kwon IH, Cho HJ, Kim KH, et al. Hydroxychloroquine-induced hyperpigmentation. J Dermatol. 2012;39:859-60.

12. Morrison LK, Nordlund JJ, Heffernan MP. Persistent cutaneous hyperpigmentation due to hydroxychloroquinone one year after therapy discontinuation. Dermatol Online J. 2009;15:15.

13. Melikoglu MA, Melikoglu M, Gurbuz U, Budak BS, Kacar C. Hydroxychloroquine-induced hyperpigmentation: a case report. J Clin Pharm Ther. 2008;33:699-701.

14. Rood MJ, Vermeer MH, Huizinga TW. Hyperpigmentation of the skin due to hydroxychloroquine. Scand J Rheumatol. 2008;37:158.

15. Amichai B, Gat A, Grunwald MH. Cutaneous hyperpigmentation during therapy with hydroxychloroquine. J Clin Rheumatol. 2007;13:113.

16. Millard TP, Kirk A, Ratnavel R. Cutaneous hyperpigmentation during therapy with hydroxychloroquine. Clin Exp Dermatol. 2004;29:92-3.

17. True DG, Bryant LR, Harris MD, Bernert RA. Clinical images: Hydroxychloroquine-associated mucocutaneous hyperpigmentation. Arthritis Rheum. 2002;46:1698.

18. R. M. Ings. The melanin binding of drugs and its implications. Drug Metab Rev. 1984;15:1183.

We use and utilize cookies and other similar technologies necessary to understand, optimize, and improve visitor's experience in our site. By continuing to use our site you agree to our Cookies, Privacy and Terms of Use Policies.