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CASE REPORTThird Time the Charm in Rosacea DiagnosisThis patient's acne eventually affected the cornea. His glaucoma medication complicated the diagnosis. Lisa Chan, O.D. Angela A. Tam, O.D. New York Sidebars:
A 55-year-old white male presented complaining of bilateral grittiness, dryness, burning and redness for approximately 1 week. He also complained of mild tenderness of the adnexa and watery discharge. The patient said he had not recently changed soaps, detergents, lotions or hair care products. One month earlier, we initiated treatment with Timoptic-XE (timolol maleate) 0.5% O.U. for primary open angle glaucoma. The patient's medical history was significant for acne rosacea, type II diabetes mellitus, chronic back pain, hyperlipidemia and depression. Medications included glyburide, Valium (diazepam) and Prozac (fluoxetine). He had no known drug allergies. Diagnostic Data Best-corrected visual acuity was 20/25 O.D. and 20/40 O.S. Motilities were full and unrestricted, pupils were normal and confrontational fields were full O.U. We observed skin telangiectasias and rhinophyma under normal lighting (figure 1).  Slit lamp examination revealed
telangiectatic vessels of the lid margins, meibomian swelling O.U., and mixed
follicles and papillae on the palpebral conjunctiva O.U. We also noted the
following in both eyes: palpebral and bulbar hyperemia that was greatest
inferiorly (figure 2), inferior corneal staining and raised subepithelial
fibrotic nodules (figures 3 and 4). There was no edema or infiltrate in either
eye, and both irises and anterior chambers were clear. 1. Typical telangiectatic vessels on the nose of this patient with acne rosacea. Intraocular pressures were 12mm Hg O.D. and 11mm Hg O.S. Dilated examination revealed mild nuclear sclerosis of both crystalline lenses and a clear vitreous O.U. The optic nerves showed distinct margins with the following cup sizes: 0.50 with a temporal slope and an acquired optic cup pit in the right eye, and 0.65 with a thin temporal rim in the left. Both maculas were flat and clear, and the peripheral retinas were healthy. Diagnosis We initially diagnosed a toxic reaction to timolol and/or its preservative, benzododecinium bromide. We discontinued  the Timoptic-XE, initiated
erythromycin ointment for antibiotic prophylaxis and told him to use
preservative-free artificial tears. The patient returned 2 weeks later with no relief. At this visit, the slit lamp exam still revealed hyperemia inferiorly, inferior corneal subepithelial fibrotic nodules and lid telangiectasia. 2. Bulbar and palpebral hyperemia O.D. before treatment. These signs are greatest inferiorly. The left eye had similar findings. We now suspected an allergic/hypersensitivity reaction. We discontinued the erythromycin and initiated Maxitrol (neomycin, polymyxin B and dexamethasone) suspension qid O.U. and Maxitrol ointment applied to the lids and lashes qhs O.U. We also instructed the patient to apply cold compresses bid and continue using the artificial tears. A month later, the patient still had no relief. Slit lamp examination once again revealed lid and conjunctival hyperemia and meibomian swelling O.U. Corneas were positive for inferior punctate staining and subepithelial fibrotic nodules. We now realized that the patient's acne rosacea transformed into rosacea keratoconjunctivitis. We also suspected that topical timolol and/or it's preservative initiated this transformation. Treatment and Follow-up  We now discontinued both forms of Maxitrol, initiated treatment with doxycycline 100mg tabs p.o. bid, reinstituted the erythromycin ointment applied to lids/lashes qhs O.U., and continued with preservative-free artificial tears O.U. We also educated the patient on lid hygiene and instructed him to start warm compresses bid for 10 minutes, lid scrubs and lid massage O.U. 3. Inferior corneal staining in the left eye. The right eye presented similarly. A month later, the patient reported an improvement in symptoms. Bulbar and palpebral hyperemia decreased, as did corneal staining. We kept him on the same dose of doxycycline for another 2 months, and then decreased the dose to 100mg tabs p.o. qd. We also alternated erythromycin and bacitracin ointments each month to prevent bacterial resistance, and initiated Alphagan (brimonidine) 0.2% bid. At the patient's last follow-up, ocular signs and symptoms were much improved and are now stable. He still has some mild inferior corneal staining and lid telangiectasia O.U. (figure 5), and is on a maintenance dose of doxycycline. We also sent him for a dermatology consult for the rosacea. Discussion  Acne rosacea is a chronic inflammatory dermatologic disease characterized by disorganization and vasodilatation of the upper dermis of the skin.1 The sebaceous glands of the nose, cheeks, and eyelids are selectively involved. Acne rosacea occurs mostly in middle-aged and older individuals, and in women more than men.1 Uncontrolled studies have reported an association between rosacea and Helicobacter pylori.2,3 Recent studies, however, have shown no statistical significance between rosacea patients who have H. pylori vs. control subjects, or between patients treated for both conditions and control subjects.4-8 4. Raised subepithelial fibrotic nodule on the inferior cornea O.D. The left eye presented similarly. About half the patients with acne rosacea develop rosacea keratoconjunctivitis, in which the rosacea symptoms affect the cornea and conjunctiva.1 Meibomian glands secrete excess sebum, orifices become inspissated and inflamed, and patients may experience burning, tearing and corneal compromise. (See also Findings in Acne Rosacea and Rosacea Keratoconjunctivitis.) We know little about how or why this transformation occurs. One hypothesis: An unknown antigen, possibly from the diseased eyelids or facial skin, reaches the eye via the tear film and penetrates the corneal epithelium, which itself becomes compromised by free fatty acids.9 This, in turn, initiates an inflammatory cascade. Also, the increased concentration of CD1 and CD4 cells in patients with acne rosacea increases the risk of this inflammatory cascade following the introduction of any exogenous stimulus.  Anecdotal evidence suggests that topical medications and/or their preservatives may be one such stimulus that can initiate the inflammatory cascade. Topical medications are known to change the pH or tear film composition. This alters the superficial layers of the conjunctival epithelium, allowing the antigen to penetrate.9 5. The right eye after treatment with doxycycline tabs p.o. Despite the continued mild hyperemia, the presentation is much improved. The left eye presented similarly. Also, beta blockers have been shown to cause corneal anesthesia and decreased tear production in certain individuals.9,10 In patients with acne rosacea, this may be enough to initiate the inflammatory cascade leading to rosacea keratoconjunctivitis. We suspect timolol was responsible for this patient's condition, but this has not been documented in the literature. Some patients may develop rosacea keratoconjunctivitis without the introduction of an exogenous stimulus. Either way, when you see a patient with acne rosacea, you must consider rosacea keratoconjunctivitis in your differential diagnosis when you observe conjunctival and corneal changes. You also must rule out allergic and toxic reactions (See Differential Diagnosis: Toxicity vs.. Allergic Reaction). Treatment of acne rosacea starts with the patient avoiding exogenous stimuli such as food or beverages that are known to exacerbate rosacea (See Stimuli that Exacerbate Acne Rosacea, Initiate Rosacea Keratoconjunctivitis). Metronidazole cream 0.75% or 1.0% formulation qd are used to treat the skin lesions.1,11,12 Azelaic acid 20% cream was shown in a recent study to be as effective as metronidazole cream 0.75% in treating inflammatory lesions.13 Low-dose isoretinoin has also been shown to treat these resistant skin lesions in cases where metronidazole cream is not effective.14,15 Treatment of ocular rosacea includes warm compresses, lid scrubs and preservative-free artificial tears if dry eye is a component. Some practitioners prescribe erythromycin ointment for prophylaxis. When the initial treatments don't provide relief, you may need to resort to tetracycline 250mg p.o. qid or doxycycline 100 mg p.o. bid for 3-6 weeks, and then taper the dosage as symptoms resolve.1,12,14 The mechanism by which the oral antibiotics relieve the symptoms is unknown. Two possibilities: Oral antibiotics affect the secretion of sebum, or they influence the interaction of the sebaceous glands with bacteria.1,14 Patients may need low-dose maintenance therapy for continuous symptomatic relief.12 The dosage necessary to keep flare-ups in remission varies according to each patient. Topical corticosteroids may be indicated in patients with concurrent conjunctivitis, episcleritis and keratitis.1,14 Arriving at the patient's diagnosis is sometimes anything but straightforward. As clinicians, we make some tentative diagnoses only to arrive at a very different one later. In a case such as this one, great patience is required on the part of both you and the patient, but eventually you both benefit from doing this clinical work. Dr. Chan practices at The Lighthouse International, a low vision service in New York. Dr. Tam is on staff at University of California at Berkeley College of Optometry and practices at a private practice. They saw this patient at the Veterans Affairs Connecticut Health Care System-West Haven Campus.
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© Review of Optometry OnLine November 15, 2000 |
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