Topical Doxepin Significantly Decreases Itching and Erythema in the Chronically Pruritic Burn Scar

Robert H. Demling, MD, Leslie DeSanti, RN


Wounds. 2003;15(6) 

In This Article

Abstract and Introduction

The chronically pruritic burn wound is an incapacitating problem. Itching, which can last months to years, is most common in a burn that required three to four weeks to heal. The incidence of chronic itch in burn scars has been reported to be up to 80 percent of patients. Chronic inflammation is likely present in a wound still itching beyond four months. Increased release of histamine from local wound mast cells and/or increased sensitivity of sensory nerves to local histamine release is considered a major causative factor. The current standard approach for chronic itch, which consists of oral antihistamines, skin moisturizers, and sedatives, is often ineffective. Doxepin is a tricyclic compound found to have extremely potent antihistamine properties. A five-percent doxepin cream is used to control the histamine-induced itch of atopic dermatitis, urticaria, and other pruritic skin disorders, including more acute burn wounds. The authors' purpose was to test the efficacy of doxepin cream in controlling post-burn itch in outpatients with healed chronically itching burn wounds of four months to one year in duration. Patients were randomized into a standard of care group using oral antihistamines or the use of topical doxepin. The study was continued over a three-month period or until the itch ceased. A 0-to-10 itch scale, 10 being the worst and a 0-to-3 erythema scale, 3 being the worst, were used in this randomized prospective trial. The authors found that itch and erythema were 5±2 and 2±1, respectively, with standard care; values were significantly decreased to 2±1 and 1±1, respectively, with the doxepin cream compared to standard care, for the length of the study period. Itching ceased in 75 percent of patients using doxepin cream before the end of the three-month period compared to only 20 percent of patients using the oral antihistamines. Mild and transient somnolence was seen in 10 percent of patients using the doxepin cream, compared to 50 percent of patients using standard care. The authors concluded that the five-percent doxepin cream significantly decreases itching and erythema in the healed, chronically itching, burn wound compared to oral antihistamines.

Severe pruritus or itching is a common and disabling problem in patients with a healed burn wound and affects 40 to 50 percent of burn patients.[1,2,3,4] Itching is most common in a burn that takes over three weeks to heal.

The chronically pruritic burn wound markedly impairs quality of life for the burn victim, and itching can last for well over a year. The mechanism is not clearly defined, but increased histamine release from the wound is a likely etiologic factor, as is the case with a number of other skin disorders.[1,2,3,4]

The source of the histamine would be the increased mast cell population typically present in the chronically pruritic wound.[5,6] Any wound 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.[8,9,10,11] 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 that are extremely sensitive to histamine have also been reported.[10,11,12] Histamine also increases surface wound blood flow, which would explain the raised red surface usually present on the chronically itching wound.[1,2,3,4]

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 chronically itching burn patients.[1,2,3,4,5,6,7,13,14]

Doxepin, a tricyclic compound used for clinical depression, has been found to have very potent H1 and H2 histamine receptor blocking properties.[15,16] Doxepin, which is currently available in a five-percent topical cream (Prudoxin®, Healthpoint, Fort Worth, Texas), 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 skin disorders. Although plasma levels of doxepin usually are not detected, some somnolence has been reported in about 10 percent of patients while using doxepin.[17,18,19,20]

The authors recently reported doxepin cream to be highly effective in controlling the itching and erythema of more acute pruritic burn wounds up to three months from time to healing.[21,22] Also, doxepin use eliminated the itch stimulus in over half the wounds prior to the end of the three-month period indicating an attenuation of the causative stimulus. Oral antihistamines had a minimal effect. Although data is lacking, the authors would expect the chronic pruritic burn to be more refractory to management, which, therefore, deserves a separate study.

The purpose of this study was to determine whether doxepin cream would be effective for controlling itch and erythema compared to oral antihistamines and sedatives. The authors studied patients currently being managed in the authors' outpatient burn clinic. The initial body burn had to be less than 35 percent of total body surface, as larger burns have prolonged wound-related discomfort, which would be difficult to separate from itch. Pruritic wounds had to be healed for at least four months.

The pruritic burns were partial thickness in depth and required three to four weeks to heal.[1,2,3,4,5] Deeper burns are excised and grafted, and these wounds in general are not a cause of chronic pruritus.

Finally, the authors studied patients already complaining of itch and already using an antihistamine, as the focus of this study was treatment, not prevention.