Topical Doxepin Cream is Effective in Relieving Severe Pruritus Caused by Burn Injury: A Preliminary Study
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Severe pruritus or itching is a common and disabling problem in patients after burn injury.1–5 The mechanism is not clearly defined, but increased histamine release from the healed wound appears to play a role. Current standard of care is the use of antihistamines. Wound erythema is also typically found.5,6 The increased mast cell population in the burn wound is likely the source.1–5 It is known that histamine release occurs from a healed wound with minimal wound manipulation and is further exacerbated by increased skin temperature.5–8
Histamine then appears to trigger local wound surface pain fibers, likely C fibers, through activation of H1 receptors. Since itch is considered a form of pain, the same fibers are felt to produce both itch and burn wound pain.5–9 In addition, there are a number of studies indicating that histamine release in burn scar will actually increase the degree of erythema and scar, which appears to further increase itching.10,11
The pruritus is often refractory to standard management, which includes oral antihistamines, skin moisturizers, and often the addition of opioids, sedatives, and pressure garments, the latter felt to decrease histamine release.1–3 Less than 20 percent of burn patients with severe itch obtain satisfactory control with these approaches, resulting in a significant level of discomfort and decreased quality of life. There is no current effective treatment for this problem.1–5 Topical corticosteroids are not used on newly healed burns due to the risk of thinning of the skin and risk of infection.
Doxepin, a tricyclic compound, has been found to have potent histamine receptor blocking properties.12–14 Doxepin, currently available in a five-percent topical cream, has been found to be approximately 50 times more potent than hydroxyzine and nearly 800 times more potent than diphenhydramine as an antihistamine. Doxepin cream has been found to control the pruritus of atopic dermatitis, eczema, and urticaria—all histamine induced—with results superior to the use of steroid cream or oral antihistamines.10–12,15 Serum levels using the cream are usually immeasurable but when detected, are over 25 times lower than the serum level required for the doxepin to have any therapeutic central nervous system activity.16,17
Our objective was to test the efficacy of doxepin cream* in patients with burn wound pruritis not controlled adequately by standard treatment modalities.
All burn patients initially admitted and now being followed as outpatients were considered candidates if inclusion criteria were met. The patient criteria included: age between 18 and 55 years and deep burns covering 10 to 40 percent of body surface. Deep burns larger than 40 percent of body surface are a much smaller patient group and have many more recovery issues. These patients typically require inpatient rehabilitation for the early burn scar period that we were testing. Secondly, the pruritic burn wound had to be totally reepithelialized for at least two months so as not to confuse pain of open areas with itching. Third, itching was present while using a standard care regimen, since this study focused on treatment not prevention. Finally, patients had to be willing to completely stop one therapy, except pressure, while the effects of a second therapy were being tested.
Twenty patients with healed burn wounds that had been healed for two to six months, and were being managed in an outpatient setting, were studied. Fifteen had at least one excision and skin grafting procedure for deeper burn areas. All patients had significant pruritus in portions of their wounds for at least two weeks, despite standard care, i.e., skin moisturizers, oral antihistamines, and sedatives, and in 10 of the patients, pressure garments.
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