Allergic contact blepheroconjunctivitis with phenylephrine eyedrops ­the relevance of late readings of intradermal tests

Allergic reactions to midriatic eyedrops are rare despite extensively used by ophthalmologists. Phenylephrine is responsible for 54-95 % of cases reported in literature. We present the case of a 56-year-old man with blepharoconjunctivitis after instillation of phenylephrine 5 %, tropicamide 0.5 %, oxibuprocaine eyedrops. The patient reported good tolerance to the mentioned drugs. Immediate readings of prick and intradermal tests, performed with the suspected drugs, were negative. Late readings (48 and 72 hours) of epicutaneous tests were also negative. At 72 hours, prick and intradermal tests to phenylephrine were positive. Allergic blepharoconjunctivitis to phenylephrine was diagnosed. Phenylephrine is an extensively used midriatic that can act as a potent sensitizing agent and can be the cause of allergic contact reactions in exposed patients. With this case we illustrate the relevance of late readings of intradermal tests in the diagnosis of late hypersensitivity drug reactions. The authors discuss about possible mechanisms responsible for negative results of epicutaneous tests.

Las reacciones alérgicas por colirios midriáticos son raras, a pesar de lo ampliamente usados por los oftalmólogos. La fenilefrina es responsable del 54-95% de los casos publicados. Presentamos el caso de un varón de 56 años, con blefaroconjuntivitis tras la instilación de un colirio compuesto de fenilefrina 5%, tropicamida 0,5% y oxibruprocaina. El paciente había tolerado anteriormente estos medicamentos. La lectura inmediata de las pruebas cutáneas (prick e intradermo) efectuadas con esos medicamentos, fue negativa. La lectura tardía (48 y 72 horas) de los tests epicutáneos también fue negativa. A las 72 horas, la prueba con fenilefrina, tanto el prick como la intradérmica, fue positiva. Por ello, el diagnóstico fue blefaroconjuntivitis alérgica por fenilefrina. La fenilefrina es una midriático ampliamente usado que puede actuar como agente sensibilizante, causando reacciones alérgicas de contacto en los pacientes expuestos. Este caso ilustra sobre la relevancia de la lectura tardía de las pruebas cutáneas para el diagnóstico de las reacciones tardías de hipersensibilidad. Se discuten los posibles mecanismos responsables de los resultados negativos de las pruebas epicutáneas.

INTRODUCTION

Allergic reactions to midriatic eyedrops are rare despite extensively used by ophthalmologists, occurring in only 6 % of total reactions associated to eyedrops¹. This may result from preservatives, additives (sodium metabisulfite, benzalkonium chloride, tetracaine, echothiophate iodide) as well as from the drug itself^2-6.

Phenylephrine is responsible for 54-96 % of all cases referred in literature^7-10.

CASE REPORT

A 56-year-old man, without personal or familial history of allergic diseases, was admitted in 2005 for retinal detachment and was diagnosed left eye melanoma. Two hours after the instillation of phenylephrine 5 %, tropicamide 0.5 % and oxibuprocain eyedrops the patient developed intense conjunctival hyperemia, with erythema and oedema of the eyelids and persistent foreign body sensation. The reaction resolved 8h after treatment unknown to the patient. Because of recurrence of symptoms after instillation of the same drugs, the patient was referred to our outpatient clinic for further investigation. Previously, the patient underwent ocular examination using midriatic eyedrops, uneventfully.

We performed skin prick tests with the commercial formulations of the drugs mentioned above, intradermal tests (1:100 and 1:10 concentrations) and patch tests (1:100, 1:10 and 1:1 concentrations). Patch tests with European standard series (True Test^®) were also performed.

At 72 hours skin prick and intradermal tests to phenylephrine were positive (duplication of the mean diameter of the papule). The other results can be seen in table I.

According to the clinical history and results from skin tests we considered diagnostic provocation with phenylephrine unnecessary. The patient had no clinical symptoms with topical instillation of tropicamide and oxibuprocain, latter on.

Phenylephrine seems to be the culprit drug in this case report.

The patient and ophthalmologist were informed to avoid phenylephrine use.

DISCUSSION

Phenylephrine is a sympathomimetic amine that is formed by a benzene ring with an OH radical in position 3 and a lateral chain of etilamine.

It is an extensively used midriatic in ophthalmology that can act as a potent sensitizing agent and can be the cause of allergic contact reactions in exposed patients^1-6.

In the study of late cutaneous hypersensitivity reactions associated with phenylephrine, as with other drugs not present in the standardized battery of allergens of the European Society of Contact Dermatitis, there still exists discussion and controversy on the concentrations, vehicles and where patch tests should be performed^11,12.

Until this moment, the predictive value of a negative patch test is unknown. In this situation, some authors recommend to perform simultaneous late readings of intradermal tests with culprit drugs.

In this case report all patch tests performed were negative, which can be due to: 1) use of an inadequate vehicle, in this case sodium chloride; 2) low drug concentration and 3) reduced cutaneous absorption.

Although the patient refused to do biopsy of skin lesions, the majority of case reports describe type IV hypersensitivity reactions with perivascular infiltrates of lymphocytes and eosinophils¹³.

The authors emphasize the relevance of simultaneous late readings of patch and intradermal tests. Therefore, if the latter are positive, they can help in final diagnosis, as in our report.

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Correspondence:
Carmen Maria da Costa Botelho
Serviço de Imunoalergologia
Hospital de São João
Alameda Professor Hernâni Monteiro
4200 Porto. Portugal
e-mail: [e-mail]