Pruritis possibilities narrowed

July 1, 2005

Boston — Determining which mediators are released in different inflammatory conditions may help dermatologists find the most effective way to treat itch, according to John Ansel, M.D. Researchers are making progress to understanding the pathophysiology of pruritus and applying it to patients, but both areas continue to require additional study, he adds.

Boston - Determining which mediators are released in different inflammatory conditions may help dermatologists find the most effective way to treat itch, according to John Ansel, M.D. Researchers are making progress to understanding the pathophysiology of pruritus and applying it to patients, but both areas continue to require additional study, he adds.

"We still don't have a real handle on what precisely causes itch," he says, "and our treatments are still unsatisfactory." However, some recent studies have provided some interesting insights.

What triggers itch? Dr. Ansel, professor of dermatology, Feinberg School of Medicine, Northwestern University, Chicago, presented a seminar reviewing current schools of thought on the pathways that trigger how the brain can sense itch at the American College of Allergy, Asthma & Immunology Annual Meeting, here.

It has been proposed that there may be specific itch fibers that are a unique subpopulation of sensory nerves in the skin. On the other hand, the itch sensation may be mediated by the release of specific types and combinations of pruritogenic mediators that can activate most sensory nerves in the skin. In other words, specific mediators rather than unique itch fibers may be responsible for pruritus. Another possibility is that pruritus may be mediated by both of these mechanisms.

"The activation of cutaneous sensory fibers may not only lead to the sensation of itch and pain but the released neuropeptides may act on adjacent epidermal and dermal cells to mediate certain inflammatory and wound healing responses," Dr. Ansel says. "In this way, the rapid activation of the cutaneous sensory nerves can initiate a range of protective immune responses which can be helpful in mediating tissue repair after injury and to defeat potential pathogens that have breached the barrier of the skin."

Toxic metabolic by-product?It has also been proposed that the pruritus that accompanies some renal or liver disorders may be the result of toxic metabolic by-product deposited on the skin, which may act on sensory nerves to incite itch. There are also some neurological conditions in which injury to the peripheral or central nervous system is accompanied by persistent pruritus. The pathophysiology of this type of pruritus is poorly understood and treated.

Itch can be so intolerable in some patients that they will scratch their skin until it is excoriated and bleeds.

"Scratching in such a vigorous fashion substitutes pain for itch, which is much more tolerable to some people," Dr. Ansel says. In contrast to effective therapies for pain such as opioids, the current treatment for pruritus is unsatisfactory.

Treatment options Dr. Ansel explains that current pruritus treatments, such as topical and systemic antihistamines and steroids primarily inhibit the inflammatory component of itch. These agents are slow acting and, although sometimes helpful, they are often ineffective in rapidly blocking the itch sensation. For example, antihistamines are thought to act primarily on mast cells. Although there is much evidence that mast cells play an important role in itch, they are not the only source of pruritogenic agents in the skin. Therefore, inhibiting mast cells alone may not relieve itch due to multiple causes.

Other non-specific modalities used in treating itch include UV light and counter irritants such as phenol and menthol that are thought to block or interfere with the itch sensation in the skin and can be helpful in certain situations. Oral charcoal has also been used for treating the pruritus that accompanies certain renal and liver disorders. The rationale for this approach is that the oral charcoal will work in the gut to somehow absorb various metabolic toxins that may mediate pruritus in these conditions. Although sometimes helpful, this treatment is often ineffective. A rapidly acting, nonspecific, nontoxic topical and systemic antipruritic agent still does not exist.

Researchers at Wake Forest University suggest itch is classified in three ways. Peripheral pruritoceptive itch, neuropathic itch or damaged nerve fibers, and neurogenic itch or itch without nerve damage and originating in the central nervous system.