Topical Doxepin Significantly Decreases Itching and Erythema in the Healed Burn Wound
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Severe pruritus or itching is a common and disabling problem in patients with healed burn wounds. Itching is most common in burns that take about three weeks to heal. The mechanism is not clearly defined, but increased histamine release from the wound is a major etiologic factor, as is the case with a number of other skin disorders.1–4
The source of the histamine would be the increased mast cell population typically present in the healed burn wound.5,6 Any wound itching, manipulation, or increase in wound temperature exacerbates the itching.
The mechanism of the itch is considered to be the activation of the wound surface C nerve fibers.8–11 The C fibers are typically considered to be pain fibers, and itch has been categorized as a form of pain.8,9 Itch nerve fibers, extremely sensitive to histamine, have also been reported.10–12
There are also a number of studies indicating that histamine increases surface wound blood flow, which may explain the erythema usually present in the itching wound.1–4
The current standard pharmacologic management of itch is the use of oral antihistamines with the frequent addition of sedatives. However, this approach is successful in less than half of the burn patients with itch.1–7 Other approaches, such as massage therapy and cool baths, are only transiently beneficial, and the continued itching may result in significant levels of discomfort and impaired quality of life.13,14
Doxepin hydrochloride (HCl) is one of a class of agents known as dibenzoxipine tricyclic compounds used for clinical depression. Doxepin has also been found to have very potent H1 and H2 histamine receptor blocking properties.15,16 Doxepin HCl is currently available in a five-percent topical cream (Prudoxin®, Healthpoint, Ltd., Fort Worth, Texas). Each gram contains 50mg of doxepin HCl. Doxepin has been found to be approximately 50 times more potent than hydroxyzine and nearly 800 times more potent than diphenhydramine as an antihistamine.15,16 Doxepin cream has been found to control the pruritus of atopic dermatitis, eczema, urticaria, and other dermatological disorders, with results superior to the use of more standard oral antihistamines.15–20 Serum levels of doxepin with the use of the cream in these disorders are usually immeasurable but, when detected, are over 25-fold lower than the serum level required for the doxepin to have any therapeutic effect on central nervous system function.17–19
The purpose of this study was to determine whether doxepin cream would be effective for controlling itch and erythema in the burn wound. A preliminary study has shown considerable success.21
The authors elected to study minor and moderate burn injuries managed in the outpatient burn clinic, as larger burns would likely have wound-related discomfort, which would be difficult to separate from itch.
The burns were to be partial thickness in depth and require two to four weeks to reepithelialize, because these are the most likely wounds to itch.1–5 It is the authors’ policy to excise and graft deeper dermal burns, i.e., those likely to require more than four weeks to heal because of the poor quality of the healed skin.
The authors studied patients already complaining of itch and using antihistamines, because the focus of this study was treatment not prevention.
Minor burn patients being followed in the outpatient clinic who complained of itch in their healed wounds were candidates for this approved study. Criteria were that the burn wounds be between six weeks and three months old, as peak itching is usually evident during this period in burns mid-dermal in depth. The burns would also have to be completely reepithelialized. In addition, the pruritic wounds could not exceed 15 percent of total body surface.
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