点击显示 收起
1 UCSD Department of Ophthalmology, UCSD School of Medicine, La Jolla, CA 92093-0946, USA
2 UCSD Department of Pathology, UCSD School of Medicine, La Jolla, CA 92093-0946, USA
3 Division of Ophthalmic Plastic and Reconstructive Surgery, UCSD Department of Ophthalmology, UCSD School of Medicine, La Jolla, CA 92093-0946, USA
Correspondence to:
Don O Kikkawa
MD, UCSD Department of Ophthalmology, Shiley Eye Center, 9415 Campus Point Drive, La Jolla, CA 92093-0946, USA; dkikkawa@ucsd.edu
Accepted for publication 15 March 2005
Keywords: conjunctiva; pigment; tetracycline
There have been no reports, to our knowledge, of a clinical presentation of ocular pigmentation secondary to the use of oral tetracycline only. Tetracycline hydrochloride is not a well recognised cause of ocular pigmentary changes, but has been reported to cause pigmentation of teeth and nails.1 Of all the tetracyclines, minocycline (a second generation drug) is most often associated with the adverse effect of pigmentation.1 There have been several case reports of minocycline induced scleral pigmentation.2–6 Ocular pigmentary changes reportedly caused by tetracycline have been noted in association with use of minocycline.7,8 Both patients in these case reports had had tetracycline/minocycline therapy for more than 10 years for acne vulgaris and had their deposition localised within the tarsal conjunctiva.7 It is believed that most of the cysts are found at the inferior border of the lower tarsus because of the frequency of pre-existing invaginations of conjunctival epithelium in this location.7 The question was raised that long term tetracycline has an effect on the lipid layer of the tear film; noting that the pigmentary deposits were only seen in the conjunctival cysts over the tarsal conjunctiva.8 Recently, there has been a case report of a patient with a 5 year history of minocycline use for rheumatoid arthritis who developed focal palpebral conjunctival pigment deposits. This patient did not have a reported use of tetracycline.2
Our patient was taking only tetracycline without concomitant or previous minocycline use and had bulbar conjunctival lesions. Our patient had also been on tetracycline for 2 years.
Case report
A 48 year old healthy white asymptomatic man presented for evaluation of "green crystals" on the conjunctiva of both eyes (fig 1). The patient had noted the onset of this pigmentation over the previous several months. The patient was treated for acne vulgaris with tetracycline 500 mg a day for the past 2 years. He denied the use of any topical ophthalmic drops. He took Lotensin for the treatment of hypertension. Past medical history was otherwise unremarkable.
Figure 1 Clinical photograph of the conjunctival pigmentary deposits.
On examination the patient was noted to have several dark green granular deposits on the temporal bulbar conjunctiva of both eyes. The granules appeared discrete, crystalline, and varied in size. Otherwise, the examination was unremarkable. Pigmentation was not noted in any other region.
Pathology
Pathology confirmed the presence of tetracycline. The specimen was positive for a non-polarisable foreign material in a submucosal and intraepithelial distribution (fig 2). This material was calcified and had a faint brown-yellow tinge. There was no appreciable inflammatory reaction or giant cell reaction to the material. Pathology was consistent with that of previously described reports of tetracycline.7
Figure 2 Light microscopy of the pathology specimen of the conjunctival biopsy showing a non-polarisable foreign material in a submucosal and intraepithelial distribution.
Comment
Tetracyclines of the first generation (tetracycline, oxytetracycline, and tetracycline chloride) are the most commonly prescribed oral antibiotics for acne.9 Tetracycline has also been shown to result in improvement of the ocular manifestations of rosacea.10,11 Both conditions are frequent; thus, the ophthalmologist will encounter many patients being treated with tetracycline. Tetracycline fluorescence has been detected in the conjunctiva of all patients who have taken tetracycline orally.12 Fluorescence was not generalised but was restricted to a thin film-like layer on the surface and to small areas in the surface layer of cells.12
This is the first case report, to our knowledge, of clinically visible conjunctival bulbar deposits caused by the use of tetracycline without a history of minocycline use. Pigmentary changes may initially be noted by the ophthalmologist, as in our case report.
It is important to recognise signs of tetracycline pigmentation as it is a commonly used medication, and cessation of the medication may help avoid further pigmentary changes.
References
Eisen D, Hakim MD. Minocycline-induced pigmentation; incidence, prevention and management. Drug Safety 1998;18:431–40.
Bradfield YS, Robertson DM, Salomao DR, et al. Minocycline-induced ocular pigmentation. Arch Ophthalmol 2003;121:144–5.
Morrow GL, Abbott RL. Minocycline-induced scleral, dental, and dermal pigmentation. Am J Ophthalmol 1998;125:396–7.
Fraunfelder FT, Randall JA. Minocycline-induced scleral pigmentation. Ophthalmology 1997;104:936–8.
Sabroe RA, Archer CB, Harlow D, et al. Minocycline-induced discolouration of the sclerae. Br J Dermatol 1996;135:314–16.
Angeloni VL, Salasche SJ. Nail, skin, and scleral pigmentation. Cutis 1987;40:229–33.
Messmer E, Font RL, Sheldon G, et al. Pigmented conjunctival cysts following tetracycline/minocycline therapy. histochemical and electron microscopic observations. Ophthalmology 1983;90:1462–8.
Brothers DM, Hidayat AA. Conjunctival pigmentation associated with tetracycline medication. Ophthalmology 1981;88:1212–15.
Zouboulis CC, Piquero-Martin J. Update and future of systemic acne treatment. Dermatology 2003;206:37–53.
Del Rosso JQ. A status report on the medical management of rosacea: focus on topical therapies. Cutis 2002;70:271–5.
Brown SI, Shahinian L. Diagnosis and treatment of ocular rosacea. Ophthalmology 1978;85:779–86.
Dilly PN, Mackie IA. Distribution of tetracycline in the conjunctiva of patients on long term systemic doses. Br J Ophthalmol 1985;69:25–8.