Topical Doxepin Significantly Decreases Itching and Erythema in the Healed Burn Wound

Author(s): 
Robert Demling, MD; Leslie DeSanti, RN

Introduction

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.

Methods

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.

References: 

References

1. Gordon M. Pruritus in burns. J Burn Care Rehabil 1988;9:305.
2. Bell L, McAdams T, Morgan R, et al. Pruritus in burns: A descriptive study. J Burn Care Rehabil 1988;9:305–11.
3. Marvin JA, Carrougher G, Bayley B, et al. Burn nursing Delphi study. J Burn Care Rehabil 1991;12:190–7.
4. Vitale M, Fields-Blache C, Luterman A. Severe itching in the patient with burns. J Burn Care Rehabil 1991;12:230–3.
5. Baker RAU, Zeller RA, Klein RL, et al. Burn wound itch control using H1 and H2 antagonists. J Burn Care Rehabil 2001;22:263–8.
6. Simone DA, Ngeow JY, Whitehouse J, et al. The magnitude and duration of itch produced by intracutaneous injections of histamine. Somatosens Res 1987;5:81–92.
7. Helvig E, Engrav LH, Cain VJ, et al. Patient’s report of itching post-burn injury. J Burn Care Rehabil 1999;20(part 2):S259.
8. Low MH, Bernhard JD. Pruritus. Semin Neurol 1992;12:374–84.
9. Schmelz M. A neural pathway for itch. Nat Neurosci 2001;4:9–10.
10. Andrew D, Craig AD. Spinothalamic lamina I neurons selectively sensitive to histamine: A central neural pathway for itch. Nat Neurosci 2001;4:72–7.
11. Greaves MW, Wall PD. Pathophysiology of itching. Lancet 1996;348:938–40.
12. Johansson O, Virtanen M, Hilliges M. Histaminergic nerves demonstrated in the skin. A new direct mode of neurogenic inflammation? Exp Dermatol 1995;4:93–6.
13. Demling R, DeSanti L, Nelson R. Pruritus and burn wounds. Wounds 2002;14(1 Suppl):2A–7A.
14. Field T, Peck M, Hernandez-Reif M, et al. Post-burn itching, pain and psychological symptoms are reduced with massage therapy. J Burn Care Rehabil 2000;21:189–93.
15. Richelson E. Tricyclic antidepressants and neurotransmitter receptors. Psychiatr Ann 1979;19:21–5.
16. Bernstein JE, Whitney DH, Keyoumars S. Inhibition of histamine-induced pruritus by topical tricyclic antidepressants. J Am Acad Dermatol 1981;5:582–5.
17. Drake LA, Fallon JD, Sober A. Relief of pruritus in patients with atopic dermatitis after treatment with topical doxepin cream. J Am Acad Dermatol 1994;31:613–6.
18. Drake LA, Millikan LE, Saber A, et al. The antipruritic effect of 5% doxepin cream in patients with eczematous dermatitis. Arch Dermatol 1995;131:1403–8.
19. Greene SL, Reed CE, Schroeter AL. Double-blind crossover comparing doxepin with diphenhydramine for the treatment of chronic urticaria. J Am Acad Dermatol 1985;12:669–75.
20. Groene D, Martus P, Heyer G. Doxepin affects acetylcholine induced cutaneous reactions in atopic eczema. Exp Dermatol 2001;10:110–7.
21. Demling RH, DeSanti L. Topical doxepin cream is effective in relieving severe pruritus caused by burn injury: A preliminary study. Wounds 2001;13(6):210–5.
22. Carr Collins J. Pressure techniques for the prevention of hypertrophic scar. Clin Plast Surg 1992;19:1735–40.
23. Kearly GP. Pharmacologic management of background pain in burn victims. J Burn Care Rehab 1995;16:388–92.
24. Marvin J. Pain assessment versus measurement. J Burn Care Rehab 1995;3:348–53.
25. Sullivan T, Smith J, Kermode J. Rating the burn scar. J Burn Care Rehabil 1990;11:256–60.
26. Freshefsky L, Tran-Johnson T. Pharmacokinetic factors affecting anti-depressant drug clearance and clinical effect: Evaluation of doxepin and imipramine—new data and review. Clin Chem 1988;34:863–80.



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