Minocycline-induced Tongue Hyperpigmentation in Treatment of Severe Keratitis & Recurrent Chalazia

1. Minocycline-induced Tongue Hyperpigmentation in Treatment of Severe Keratitis & Recurrent Chalazia Amit Todani, MD Samir Melki, MD PhD Massachusetts Eye & Ear Infirmary Harvard Medical School, Boston The authors do not have any financial interest in any of the products or companies mentioned in this poster

2. Introduction • Minocycline is occasionally used systemically in the management of meibomian gland dysfunction and/or severe keratitis. • It recently appeared in the market in a specific package combined with a lid scrub foam solution (Cleeravue-MTM, Stonebridge Pharma), which may lead to its increased use as compared to other tetracyclines. • Pigmentation at various body sites is a well recognized though innocuous side-effect, which warrants discontinuation of minocycline therapy.1 Hence, patients on chronic minocycline therapy merit screening for development of pigmentation.

3. Case Report A 27-year old Asian woman was given 100 mg of minocycline hydrochloride once daily by mouth for bilateral severe keratitis with dry eyes and bilateral recurrent chalazia (figure below).

4. Case Report (Contd.) • Other medications – artificial tears, topical cyclosporine 0.05%. • Also daily warm compress with lid massage. • No systemic conditions. • Past medical history- unremarkable.

5. Case Report (Contd.) • 2 months after starting minocycline, she noted multiple dark spots on her tongue. • Our examination revealed isolated patches of dark-grey pigmentation scattered over the tip and dorsolateral aspects of her tongue (Figure ) • These lesions were painless. No other changes were found in the oral cavity, skin or the ocular surface. Her fundus examination was unremarkable.

6. Case Report (Contd.) • Oral minocycline was discontinued because of the appearance of lingual hyperpigmentaion. • 3 months following discontinuation of her minocycline therapy, she reported partial resolution of the hyperpigmentation. • She was subsequently started on oral doxycycline (50 mg twice daily) which lead to symptomatic relief of ocular pain and redness. • Her last follow-up was 12 months after discontinuing minocycline. The lingual pigmentation was found to be persistent but much lighter in intensity.

7. Discussion • Minocycline offers some distinct advantages over other tetracyclines. It is generally well tolerated, absorbed well in the gastrointestinal tract, is highly lipophilic and has a large volume of distribution along with a long serum half life. This contributes to excellent tissue penetration with convenient once or twice daily dosing regimen. • Unlike other tetracyclines, it does not bind calcium from dairy products and is less likely to contribute to phototoxic reactions.

8. Discussion • On the other hand, minocycline has been reported to cause pigmentation in various body sites, esp. the skin, nails, bones, thyroid, mouth, sclera, conjunctiva and macula.1-4 • Lingual hyperpigmentation is rarely reported and may be easily overlooked.5-8 To the best of our knowledge, no cases have been reported in ophthalmic literature. • Many cases of pigmentary change tend to resolve spontaneously on discontinuation of the therapy. Successful treatment of a rare case of persistent pigmentation has been reported with Q-switched laser.8 • We encourage ophthalmologists to inform patients of possible muco-cutaneous and ocular discoloration with the use of minocycline therapy and to look out for this adverse effect. It is recommended to stop minocycline therapy if it is the suspected cause of the discoloration.

9. References • Eisen D, Hakim MD. Minocycline-induced pigmentation. Incidence, prevention and management. Drug Saf. 1998 Jun;18(6):431-40. • Fraunfelder FT, Randall JA. Minocycline-induced scleral pigmentation. Ophthalmology. 1997 Jun;104(6):936-8. • Bradfield YS, Robertson DM, Salomao DR, Link TP, Rostvold JA. Minocycline-induced ocular pigmentation. Arch Ophthalmol. 2003 Jan;121(1):144-5. • Morrison VL, Kikkawa DO, Herndier BG. Tetracycline induced green conjunctival pigment deposits. Br J Ophthalmol. 2005 Oct;89(10):1372-3. • Tanzi EL, Hecker MS. Minocycline-induced hyperpigmentation of the tongue. Arch Dermatol. 2000 Mar;136(3):427-8. • Meyerson MA, Cohen PR, Hymes SR. Lingual hyperpigmentation associated with minocycline therapy. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1995 Feb;79(2):180-4. • Alkhatib AA, Sessoms S. The tarnished tongue. Am J Med. 2006 Oct;119(10):832-4. • Friedman IS, Shelton RM, Phelps RG. Minocycline-induced hyperpigmentation of the tongue: successful treatment with the Q-switched ruby laser. Dermatol Surg. 2002 Mar;28(3):205-9.