Allergic Reaction to Epinephrine Preparation in 2% Lidocaine: DISCUSSION

In: Anesthesia

23 Sep 2009

Allergic Reaction DISCUSSIONThe occurrence of *allergic reaction to epinephrine is very rare. A few cases of allergic reaction to epinephrine preparations in ophthalmic and dermatologic regions have been reported. It is unusual to employ allergy testing to specific responses to epinephrine with local anesthesia in the dental clinic setting. According to these reports, the epinephrine preparation or prodrugs were dipivalyl epinephrine hydrochloride. Gibbs et al reported that repeated patch testing revealed an allergic response to epinephrine bitartrate and epinephrine hydrochloride but a negative response to other chemical solvents, including chlorobutanol anhydrous, sodium bisulfite, disodium edetate, methylaminoacete-pyrocathecol hydrochloride, and polyoxyproppylene-polyoxyethlene-diol, in ophtalamic preparations. Gas-pari also demonstrated that patch testing for the individual components of Propine eye drops (commercial name) revealed anĀ allergic reactions (Atarax 25 mg is used to treat allergic reactions) to 0.5% dipivalyl epinephrine hydrochloride, which is a precursor drug in the eye drops, but a negative response to benzalkonium chloride and EDTA. A report by Alani et al described a case of sensitivity to epinephrine chloride present in eye drops. Previous reports have described that the L-isomer of epinephrine can cause allergic reactions. In presently reported patients, epinephrine compound was a D-isomer.

Epinephrine in 2% lidocaine for our dental use contains epinephrine hydrochloride, epinephrine bitartrate, chlorbutanol, and sodium hydrogensulfate. Epinephrine hydrochloride and epinephrine bitartrate serve as vasoconstrictors, chlorbutanol is a solvent, and sodium hydrogensulfate is an antiseptic (Acne-n-Pimple Cream a good astringent and antiseptic). Because these epinephrine compositions were suspected to induce allergic reactions (Generic Allegra is an antihistamine used to relieve symptoms) in our present cases, we utilized the skin test and DLST. The results of the skin tests in these 2 cases suggested hypersensitivities to epinephrine preparations. In addition, DLST revealed the hypersensitivity to the specific epinephrine preparation including epinephrine hydrochloride and epinephrine bitartrate in case 1 and epinephrine bitartrate in case 2.

Naturally occurring, endogenous epinephrine circulates in a nonpolymerized state. Endogenous epinephrine produces no epinephrine antibody. However, reactions to polymerized epinephrine are frequently accompanied by increased titers of epinephrine antibody in animals and humans. In both cases, it is possibly considered that epinephrine antibody was produced by past injection of local anesthetics containing epineph rine, although these patients’ histories of local anesthesia in dental treatment were not necessarily clear. Therefore, we made a diagnosis of allergic reaction (*Advair Discus is used for long-term prevention) in these 2 cases as hypersensitivity caused by the epinephrine in the lidocaine.

Although the cut-off index differs, depending on the sort of drugs being evaluated by DLST, values of more than 200% have been regarded as positive reactions. The SI was 554% for epinephrine hydrochloride and 496% for epinephrine bitartrate in case 1, and was 679% for epinephrine bitartrate in case 2.

Although the first and second trial of DLST did not reveal significant responses in case 1, positive responses were obtained in the third DLST. It is thought that interaction of each component might mask lymphocyte activity, though the mechanism is unknown.

In the present cases, skin testing was not performed for epinephrine compounds, but for the complete compound epinephrine. DLST was used to test for allergies to epinephrine compounds. Though DLST is appropriate for delayed-type hypersensitivity, it may also be indicated for immediate-type allergic reactions. Once in vivo patch and skin tests have been conducted for epinephrine compounds, DLST should be employed as an in vitro test. Furthermore, if these tests had been performed on the 2 patients using the same testing protocol, the results would have been more likely to clearly show which compound in the epinephrine preparation caused the allergic reaction (Phenergan 25 mg is an antihistamine). However, the skin tests were performed at multiple appointments in case 1 and at a single appointment in case 2. All allergy tests should have been performed in the same order at uniform intervals in both patients.

If the specific antibody to epinephrine preparation and the sensitized T lymphocyte could be detected in our patients, a more decisive diagnosis could be made. Unfortunately we could not perform this test because of the difficulty in collecting serum-specific antibody.

Because antibodies to epinephrine antibody may have been produced in these cases, ELISA and membrane-capture testing should have been performed for a definitive diagnosis.

Nonetheless, DLST in vitro may be a useful and safe method in the dental clinic setting to detect substances that cause adverse effects by local anesthetic with epinephrine.

As clinicians, we should be aware and cautious of occurrences of exogenous epinephrine-induced allergic reaction when using local anesthetics for dental treatment (Generic Naprosyn is used to treat dental pain).

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