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Recent advances: combine agents to treat itch in atopic dermatitis.

WASHINGTON -- Antipruritic therapy in patients with atopic dermatitis should combine peripherally acting anti-inflammatories, immunomodulating agents, moisturizers, and centrally-acting inhibitors, Dr. Gil Yosipovitch said at the annual meeting of the American Academy of Dermatology.

Until recently, inflammation was thought to be primarily responsible for itch. Now, new pathophysiologic research suggests that there is "cross talk" between the stratum corneum and the nervous system. Damage to the skin barrier induces secretion of a variety of chemical mediators and neuropeptides, which in turn induces small nerve fibers to transmit itch. Both central and peripheral itch-specific fibers have been identified, which suggests that the process is independent of pain.

Intervention at various points could arrest the process and thereby alleviate itch. "These findings will lead to selective topical and systemic treatments for itch," said Dr. Yosipovitch of the departments of dermatology and neuroscience at Wake Forest University, Winston-Salem, N.C.

There are now several avenues of approach, Dr. Yosipovitch said:

* Drugs that target the nervous system centrally to reduce itch intensity and peripherally to inhibit itch transmission.

* Anti-inflammatories, including immunomodulators and agents that block neuropeptide receptors.

* Moisturizers, particularly the ceramide-dominants.

* Combination therapy.

For mild to moderate itch, topical steroids, tacrolimus, topical salicylates, moisturizers of various kinds including ceramide-dominants are all options, either alone or in combination. Use of agents that contain both moisturizers and topical antipruritics (such as pramoxine) or topical aspirin and salicylates with topical steroids, may be especially useful.

Topical salicylates are extremely effective in reducing itch, but have not been widely used for that purpose in the United States, as they have in Europe.

"Topical salicylates are underused in this country.... I use them often," Dr. Yosipovitch remarked.

For patients with severe nocturnal itch, consider adding mirtazapine (Remeron). In a study of 15 patients aged 12 years and older with atopic eczema, prurigo nodularis, or lichen simplex chronicus, 15 mg at bedtime significantly reduced itch intensity, with 80% of patients reporting improved sleep and overall quality of life. The agent, a noradrenergic and specific serotonergic antidepressant, is also an antihistamine.

Side effects include dry mouth, sedation, appetite stimulation, and weight gain, but not sexual dysfunction. "It's one of those safe drugs when compared with other antidepressants," he said.

Severe flare-ups or erythrodermic forms of itch may also respond to mirtazapine at night, along with wet-wrap therapy, which involves applying a topical steroid plus a moisturizer to the skin, then swaddling the patient first in a wet pajama and then a dry one. "It feels odd, but it works," he noted.

For patients who have prurigo nodularis, thalidomide may be particularly effective as an antipruritic. The agent acts as both a central nervous system depressant and an anti-inflammatory. In a study of 11 patients with various types of itch, 200 mg of thalidomide a night for 2 nights significantly reduced the itch in the prurigo patients, but less so in those with generalized atopic eczema (Acta. Derm. Venereol. 80[1]:24-25, 2000).

Unfortunately, thalidomide is extremely expensive and notoriously teratogenic. "At this point, I wouldn't recommend it for general atopic eczema. Hopefully safer derivatives will be developed soon," he said.

Dr. Yosipovitch is a consultant for Fujisawa Healthcare Inc., which markets tacrolimus under the trade name Protopic.

BY MIRIAM E. TUCKER

Senior Writer
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Title Annotation:Focus on Skin Disorders
Author:Tucker, Miriam, E.
Publication:Internal Medicine News
Geographic Code:1USA
Date:Apr 1, 2004
Words:541
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