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To Topical Ophthalmic Preparations 740 Brtish_JournalofOphshalmology 1993; 77:740-741 CASE REPORTS Br J Ophthalmol: first published as 10.1136/bjo.77.11.740 on 1 November 1993. Downloaded from Contact allergic dermatitis and contact urticaria due to topical ophthalmic preparations BF O'Donnell, I S Foulds A patient with chronic glaucoma and a history of margins. There was no evidence of conjunc- contact allergic dermatitis to topical ophthalmic tivitis. Previous patch tests with the European , adrenergic blocking drugs developed persist- standard series, a preservative series, a face and ent ocular symptoms despite avoidance of , eye series, a contact lens series, and pilocarpine blockers. He was further investigated for possible 4% eyedrop had shown a plus/minus reaction to allergy to pilocarpine. benzalkonium chloride and a plus/minus reaction to pilocarpine eyedrops which contained benzalkonium chloride as a preservative. Treat- Case report ment was changed to unpreserved pilocarpine A 70-year-old man presented with a persistent eyedrops, and his eyelids treated with a mild itch involving his eyes and a stinging and topical corticosteroid preparation. After initial sensation aggravated by instillation of improvement in the appearance and swelling of The Skin Hospital, burning George Road, his pilocarpine eyedrops. The patient had a long the eyelids the patient re-presented with a Edgbaston, Birmingham history ofglaucoma and had bilateral trabeculec- recrudescence of the burning and stinging B15 1PR tomies carried out in 1978. He still required sensation ofhis eyes. B F O'Donnell I S Foulds therapy and had been treated with (3 blockers and Patch testing with unpreserved pilocarpine Correspondence to: pilocarpine since 1984. Treatment with I6 (Minims 1%, 2%, and 4%) was negative at 2 and Dr BF O'Donnell blockers had been discontinued owing to the 4 days. Subcutaneous and intradermal testing Professorial Unit, St John's Institute of Dermatology, St development ofcontact allergic dermatitis which with unpreserved pilocarpine 4% was negative at Thomas's Hospital, Lambeth apparently developed sequentially to timolol, 2, 4, and 7 days, making delayed hypersensitivity Palace Road, London SEI 7EH. betaxolol, and metipranolol as described pre- unlikely. However, prick tests showed a positive Accepted for publication viously.' Examination revealed periorbital reaction with the development of a lOx 10 mm 22 June 1993 oedema with erythema and swelling of the lid weal at 10-30 minutes. Prick tests in seven controls (three atopic, four non-atopic) resulted in small weals measuring up to 3 mm in diameter http://bjo.bmj.com/ (four controls), or erythema only (three controls). Table I Contact allergic dermatitis due to ophthalmic 13 blockers We therefore considered that the reaction seen in our patient was significant. Pilocarpine was (3 blocker Other blockers tested Cross sensitisation Reference discontinued and substituted with levobunolol Timolol (1)* 5 Timolol (1) 6 hydrochloride. The patient's ocular and peri- Levobunolol (1) 7 ocular symptoms improved dramatically, and his 8 Levobunolol (1) on September 30, 2021 by guest. Protected copyright. Metoprolol (5) propranolol propranolol 9 intraocular pressure was 15 mm Hg in both eyes. practolol practolol timolol timolol atenolol oxprenolol Comment pindolol to sotalolol It may be difficult separate the clinical Metipranolol (1) penbutolol ? penbutolol 10 diagnoses of contact dermatitis, contact conjunc- propranolol to oxprenolol tivitis, and contact urticaria owing the betaxolol heightened sensitivity in the eye and the adjacent pindolol timolol skin.I Contact dermatitis affecting the periocular hydroxypropranolol skin may be irritant (toxic) or allergic in nature. metoprolol The be involved in similar Befunolol (1) levobunolol levobunolol 11 conjunctiva may carteolol processes3 either alone or associated with betaxolol timolol cutaneous involvement, so-called dermatocon- Befunolol (6) timolol 12 junctivitis. The conjunctiva with its lymphoid carteolol Befunolol (3) timolol 13 tissue may be involved in all immune Metipranolol (4) mechanisms.3 The allergic reaction is a delayed Befunolol (1) timolol 14 hypersensitivity response (type IV) mediated by carteolol levobunolol T lymphocytes. Antigen sensitised T cells release Timolol (1) carteolol following secondary contact with Betaxolol levobunolol presentpresetcascase lymphokines Metipranolol atenolol the same antigen. Diagnosis of type IV allergy metoprolol propranolol may be confirmed by relevant positive patch tests. False negative reactions occur when * Figures in parentheses indicate the number(s) of patients studied. percutaneous absorption is inadequate, concen- Conactalkrgicdermatisandcontacturticariaduetowpfcalopkhhalmi preparatnns 741 tration ofthe allergen is too low, or the vehicle is allergic contact and photocontact dermatitis has Br J Ophthalmol: first published as 10.1136/bjo.77.11.740 on 1 November 1993. Downloaded from inappropriate. To increase sensitivity intra- been reported.'617 Contact urticaria due to pilo- cutaneousinjectionmay becarriedout. Ifdelayed carpine has not, to our knowledge, previously hypersensitivity is suspected the results are read been reported. at 48 and 96 hours. Our patient is ofinterest because in addition to Various (3 blocking ophthalmic preparations type IV hypersensitivity to three ophthalmic (3 have been implicated in allergic contact conjunc- blockers he developed contact urticaria to pilo- tivitis4 and allergic contact dermatitis' S14 (Table carpine. He is currently using levobunolol 1). Positive allergic reactions to more than one (3 hydrochloride to control his glaucoma without blocker in the same patient have raised the showing an adverse reaction as yet. question of cross sensitivity between various (3 blockers, which has been demonstrated for some We are grateful to Ms E Kritzinger for referring the patient, and to , blockers>" and not for others.'2"'4 It is likely the following pharmaceutical companies who kindly supplied i that cross sensitisation exists between certain (3 blockers for skin testing: Alcon, Allergan, Dispersa, Merck Sharp blockers only, but the numbers reported to date and Dohme, and Smith and Nephew. are small. 1 O'Donnell BF, Foulds IS. Contact allergy to beta-blocking Contact urticaria describes a particular reac- agents in ophthalmic preparations. Contact Dermatitis 1993; tion after contact with the skin or mucous 28:121-2. 2 Herbst RA, Maibach HI. Contact dermatitis caused by allergy membranes. The prototype is the weal and flare to ophthalmic drugs and contact lens solutions. Contact response, but a spectrum exists from pruritus Dermatitis 1991; 25: 305-12. 3 Podmore P, Storrs FJ. Contact lens intolerance; allergic onlythroughwealandflare toa systemicreaction. conjunctivitis? ContactDermatitis 1989; 20: 98-103. The diagnosis ofcontact urticaria may be difficult 4 Cameli N, Vicenzi C, Tosti A. Allergic contact conjunctivitis due to timololineyedrops. ContactDermatitis 1991; 25: 129- when the eyes are involved. The weal and flare 30. response may not be apparent and the diagnosis 5 Romaguera C, Grimalt F, Vilaplana J. Contact dermatitis by timolol. ContactDermatitis 1986; 14: 248. is suggested by the symptoms of burning or 6 Fernaadez-Vozmediano JM, Alonso Blasi N, Romero-Cabrera stinging rather than the signs which are more MA, Carrascosa-Cerquero A. Allergic contact dermatitis to timolol. ContactDermatitis 1986; 14: 252. easily discernible on the skin elsewhere. 7 van der Meeren HLM, Mcurs PJ. Sensitization to levobunolol Symptoms occur early, being precipitated by eyedrops. ContactDermatitis 1993; 28: 41-2. 8 Schultheiss E. Ueberempfindlichkeitgegenueber levobunolol. instillation of the offending substance into the Derm BerufUmwt 1989; 37:185-6. eye. 9 Van Joost Th, MiddeLkamp Hup J, Ros FE. Dermatitis as a side-effect of long-term topical treatment with certain beta- Contact urticaria is classified into imimuno- blocking agents. BrJDermatol 1979; 101: 171-6. logical, non-immunological, and unknown 10 de Groot AC, Conemans J. Contact allergy to metipranolol. ContactDermatitis 1988; 18: 107-8. categories.'5 Regardless of the mechanism the 11 Corazza M, Virgili A, Mantovani L, Taddei Masieri L. final common pathway is probably the same and Allergiccontactdermatitisfromcross-reacting beta-blocking agents. ContactDermatitis 1993; 28: 188-9. eventuates in histamine and probably other 12 Kanzaki T, Kato N, Kabasawa Y, Mizuno N, Yuguchi M, mediators being released from mast cells. Majima A. Contact dermatitis due to the beta-blocker befunolol in eyedrops. Contact Dermatitis 1988; 19: 388. Immunologically triggered contact urticaria may 13 Gailhofer G, Ludvan M. 'Beta-blockers': sensitizers in peri- involve IgE mediated hypersensitivity as orbital allergic contact dermatitis. Contact Dermatitis 1990; 23:262. http://bjo.bmj.com/ indicated by a positive radioallergosorbent test 14 Mancuso G. Allergic contact dermatitis due to befunolol in (RAST). Prick or scratch tests will be positive in eyedrops. Contact Dermatitis 1992; 27: 198. 15 Greaves MW, Kaplan AP. Urticaria and angioedema. In: the affected individual and negative in healthy Samter M, Talmage DW, Frank MM, Frank Austen K, controls, in contrast to non-immunological Claman HN, eds. Immunological dismses. 4th ed. Boston/ Toronto: Little, Brown, 1988: 1187-204. contact urticaria which may be elicited in healthy 16 Ortiz FJ, Postigo C, Ivars J, Ortiz PL, Merino V. Allergic asymptomatic individuals. contact dermatitis from pilocarpine and thimerosal.
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