Doxepin

Abstract

Although allergic contact dermatitis to topical preparations of doxepin has been published (1-6, 10), systemic contact dermatitis from oral doxepin is more of a theoretical consideration and is rarely reported (2). We report a case of a patient with contact allergy to doxepin hydrochloride 5% cream who developed a systemic contact dermatitis to oral doxepin.

Case Report

A 75-year-old retired man was referred for evaluation of a chronic pruritic dermatitis of one year's duration on his scalp, axillae, trunk, lower legs, and feet. His eruption had been resistant to treatment by various medications. These included oral antihistamines, topical corticosteroids and topical antipruritics including doxepin hydrochloride 5% cream (Zonalon[R] cream, Bioglan Pharma, Inc., Malvern, PA).

Examination revealed hyperpigmented, erythematous scaly patches and plaques on the superior back, and erythematous, scaly patches and plaques on the superior chest, axillae and left calf. There was mild generalized xerosis. No dermatographism was elicited.

Current topical therapy consisted only of tacrolimus 0.1% ointment, and doxepin 25 mg was taken orally at bedtime for pruritus.

An allergic contact dermatitis was suspected and patch testing was performed to a series of 54 allergens and several of the topical medications he had used including doxepin hydrochloride 5% cream, fluocinonide ointment and tacrolimus ointment 0.1%, according to the North American Contact Dermatitis Group standard protocol. At 48 and 96 hours, a 2+ positive reaction was noted to doxepin hydrochloride 5% cream. The remainder of the patch tests were negative, except for weak 1+ reactions to nickel sulfate and thimerosal, which were not thought to be of clinical significance.

Oral doxepin was discontinued, and treatment with oral hydroxyzine and topical corticosteroids for one month resulted in marked improvement of his dermatitis.

Discussion

Our patient developed a systemic contact dermatitis to oral doxepin, to which he had been sensitized previously by topical use. The positive patch test to the doxepin hydrochloride 5% cream (Zonalon cream[R]) and his clinical improvement after discontinuation of oral doxepin support this. The inactive ingredients of the cream were not tested but are uncommon allergens. Besides Zonalon[R] cream, another commercially available product containing doxepin hydrochloride 5% is Prudoxin[R] cream, (Healthpoint, Ft. Worth, Texas.)

Doxepin is one of a class of psychotherapeutic agents known as dibenzoxazepine tricyclic compounds. Because of its known antihistamine activity blocking both H1 and H2 receptors, doxepin is used topically for its antipruritic properties. However, the capacity for sensitization to doxepin cream and other topical antihistamines limits their beneficial effects (8). Both H1 and H2 blockers such as diphenhydramine and pyribenzamine, respectively, induce allergic contact dermatitis and photodermatitis (1). Doxepin is similar in structure to the phenothiazine class of antidepressants, also known contact- and photosensitizers (1). Although initial clinical trials conducted by Drake et al. and the Doxepin Study Group (9) did not detect local hypersensitivity, a number of cases of allergic contact dermatitis caused by topical doxepin hydrochloride cream have been published (1-6,10). A total of 26 post-marketing cases of allergic contact dermatitis to doxepin 5% cream have been reported to the Food and Drug Administration; of these 81% were confirmed with a positive patch test and 65% reported a treatment duration exceeding the labeled 8 days (10). Taylor et al. (2) have added doxepin hydrochloride 5% to their standard screening tray because of the frequency of positive reactions to this topical antihistamine. Bonnel et al. (10) suggest clinicians should be aware that allergic contact dermatitis to doxepin cream may be more frequent than previously realized, especially with prolonged use, and that the possibility of allergic contact dermatitis to doxepin cream should be investigated in patients whose condition does not respond or worsens with use.

Systemic contact dermatitis may occur in contact-sensitized individuals after oral, transcutaneous, intravenous, or inhalation exposure to the allergen. Often clinically indistinguishable from other types of contact dermatitis and thus requiring a high index of suspicion to identify, features include dermatitis in areas of previous exposure, flare-ups of previous dermatitis or previously positive patch test sites, dermatitis on previously unaffected skin, pompholyx or dishydrotic dermatitis, flexural dermatitis, baboon syndrome, toxicoderma, and vasculitis-like lesions. Both humoral and cellular immune systems are apparently activated in systemic contact dermatitis; sensitized T cells may be responsible for flares of previous dermatitis sites, while a systemic cytokine release is thought to cause flexural eczema, vesicular hand eczema, baboon syndrome and toxicoderma (7).

References

(1.) Shelley WB, Shelley ED, Talanin NY. Self-potentiating allergic contact dermatitis caused by doxepin hydrochloride cream. J Am Acad Dermatol 1996; 134:143-4.

(2.) Taylor JS, Praditsuwan P, Handel D, et al. Allergic contact dermatitis from doxepin cream: One-year patch test clinic experience. Arch Dermatol 1996; 132:1-518.

(3.) Greenberg JH. Allergic contact dermatitis from topical doxepin. Contact Dermatitis 1995; 33:281.

(4.) Buckley DA. Contact allergy to doxepin. Contact Dermatitis 2000; 43:231.

(5.) Wakelin SH and Rycroft RJG. Allergic contact dermatitis from doxepin. Contact Dermatitis 1999; 40:214.

(6.) Bilbao I, Aguirre A, Vicente JM, et al. Allergic contact dermatitis due to 5% doxepin cream. Contact Dermatitis 1996; 35:254.

(7.) Veien NK, Menne T. Systemic contact dermatitis, in Rycroft RJG, Menne T, Frosch PJ, Lepoittevin J-P (eds): Textbook of contact dermatitis. 3rd ed. Berlin, Springer, 2001; 701.

(8.) Brandao FM, Goossens A, Tosti A. Topical drugs in Rycroft RJG, Menne T, Frosch PJ, Lepoittevin J-P (eds): Textbook of contact dermatitis. 3rd ed. Berlin, Springer, 2001; 701.

(9.) Drake LA, Fallon JD, Sober A, The Doxepin Study Group. Relief of pruritus in patients with atopic dermatitis after treatment with topical doxepin cream. J Am Adad Dermatol 1994; 31:613-616.

(10.) Bonnel RA, La Grenade L, Karwoski CB, Beitz JG. Allergic contact dermatitis from topical doxepin: Food and Drug Administration's postmarketing surveillance experience. JAAD 2003; 48(2): 294-296.

ADDRESS FOR CORRESPONDENCE:

Ronald R Brancaccio MD

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Phone: 212 675 5847

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RONALD R BRANCACCIO MD (1)

SARI WEINSTEIN MD (2)

(1.) RONALD O PERELMAN DEPARTMENT OF DERMATOLOGY NEW YORK UNIVERSITY SCHOOL OF MEDICINE, NEW YORK, NEW YORK

(2.) ALBERT EINSTEIN COLLEGE OF MEDICINE, BRONX, NEW YORK

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