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How to treat that nasty itch

Chronic itch is an illness in its own right, with its own symptoms, signs, and complications. It has physical, emotional, and psychosocial dimensions and, due to its complexity, is often poorly understood. Chronic itch differs from acute itch because therapies that provide relief for transient itch do not resolve the underlying pathological process. Chronic itch continues when treatment stops and can lead to drastic effects on patient quality of life (1). Most dermatologists treat itch with various antihistamines and topical anti-inflammatory medications, including topical corticosteroids and, occasionally, cooling agents such as menthol. This short review will discuss my treatment strategies and methods to deal with the debilitating symptom of itch. I will also discuss several new suggested venues to target this symptom. Understanding the pathophysiology of itch in different diseases will enable us to more effectively treat the symptom of itch. A recently proposed definition of itch characterizes it into four specific groups: (a) pruritoceptive itch, which is itch related to skin inflammation or damage to the skin barrier function; (b): neuropathic itch, which is itch related to damage to the nerve fibers along the afferent pathway; (c) neurogenic or systemic itch related to neuropeptides such as cholestatic itch without primary skin rash; and (d) psychogenic itch, which is itch caused by psychological factors. These characteristics will serve as a helpful tool to provide proper treatment (2). While there are many modalities that can be used in managing itch in patients, drug treatment remains, for the most part, the cornerstone of treatment. An important and often neglected area of treatment is targeting the nervous system, both peripherally and centrally. This is the final common pathway of itch transmission, and we believe that reducing itch intensity centrally and spinally is a prime goal of treatment. Recently, an antidepressant (NaSSA) – which is an antagonist at central presynaptic a-2 adrenergic receptors and a potent antagonist of 5-HT2 and 5-HT3 receptors – has shown antipruritic effect (3,4). We suspect NaSSA has a central effect in reducing itch through its effect on adrenergic a-2 receptors in the brain. A significant reduction of itch intensity, especially at night time, was noticed in more than 40 patients with different types of pruritus (including pruritoceptive itch such as atopic eczema, prurigo nodularis, and urticaria; systemic itch such as cholestatic and uremic itch and psychogenic itch). Another target of itch treatment is inhibition of itch transmission in the peripheral nervous system. Thalidomide, a drug that is part of our armamentarium of treatment options, has recently been found to be effective in reducing severe neuropathic pain. In addition to its well-known effect in reducing prurigo nodularis, thalidomide inhibits neuropathic itch (5,6). Its mechanism of action as an antipruritic could be three-fold. First, it has an effect in inhibition of C nerve fiber function. Second, it has an effect on the brain as a sedating agent. Thirdly, it is a potent tumor necrosis factor (TNF) inhibitor; noteworthy because TNF may be involved in itch in inflammation (7). While many of us know that pain can suppress itch, it is worth exploring whether a mechanism that induces tolerable painful stimuli can inhibit chronic itch. Counterirritants such as menthol and capsaicin work in part by this mechanism. One of our future goals is to induce pleasurable pain that can inhibit itch. Tactile stimuli of the skin is one possible technique. Tickling, in many cases, causes a pleasurable sensation; we believe that we can induce through pleasurable pain a form of itch sensation that does not induce the urge to scratch. This pleasurable sensation would, in effect, create a tolerable itch. Another recent technique using electrical nerve stimulation (which activates C nerve fiber nociceptives) may inhibit itch by a similar mechanism (8). Another possible target in treating itch involves the use of antinociceptive medications, which are not pain specific but can attenuate itch. A promising drug in development is anandamide, a peripheral cannabinoid receptor agonist, which attenuates pain and was recently found to reduce itch as well (9). Treatment of itch emanating from inflammation may benefit from efforts to target serine proteases secreted from mast cells, as well as their PAR-2 receptors located in both cutaneous nerve fibers and the epidermis. These mediators have been recently found to be four-fold elevated in atopic eczema (10). Currently, there are no commercially topical serine protease inhibitors, which have shown anti-itch properties in humans. However, an oral serine protease inhibitor used in humans in Japan as an anticoagulant demonstrated antipruritic effect in mice (11). Another potential method for treating itch in skin inflammation and dry skin is changing the milieu of ion dynamics in the stratum corneum, thus affecting skin fiber function. Skin barrier function is also predicted on ion gradient stability; serine proteases are known to be elevated in high skin surface pH (12). A change in ion flux or alteration in stratum corneum pH gradient may be a possible target for itch inhibition. The epidermis has Experimental Dermatology 2005: 14: 478–479 Copyright # Blackwell Munksgaard 2005 Blackwell Munksgaard . Printed in Singapore EXPERIMENTAL DERMATOLOGY ISSN 0906-6705