Vol. 30. No. 2


Itch, which is defined as an unpleasant sensation of the skin that leads to the desire to scratch, has a profound negative effect on the quality of life of our patients. Although pruritus (itch) is the most frequent symptom in dermatology, it remains a major clinical challenge. Itch can be produced by various inflammatory skin diseases, allergies, tumors, autoimmune diseases, metabolic diseases, neuropathic states, and psychiatric disorders, as well as being a side effect from medications. Optimal treatment is often hampered by our lack of understanding of the pathophysiology, the crucial mediators, and the failure to identify “itch receptors.” Similar to pain, itch is a sensation that derives from activation of the sensory nervous system. Sensory nerve endings in the epidermis and dermis transmit the “itch signal” via the spinal cord and spinalthalamic tract to the central nervous system. The brain also appears to be a major player in the processing and chronicity of itch. Thus, the itch that patients perceive is an integrated perception modulated at 4 levels in the nervous system: first, in the periphery; second, in the dorsal root ganglia; third, at the spinal cord level; and fourth, in the brain. Basic science research has elucidated the levels at which antipruritic agents work and provides potential new targets for drug development. Clinical and basic science research on itch is a fascinating field for new discoveries. Recent discoveries, such as new histamine receptors, histamine-independent itch pathways, including gastrin-releasing peptide, proteases, and cytokines, illustrate that itch research has entered a new era. The development of new drugs, such as calcineurin inhibitors, slow-release local anesthetics, the -opiate receptor agonists, monoclonal antibodies targeting molecules involved in itch pathophysiology (eg, anti-immunoglobulin E, anti-nerve growth factor, anti-interleukin-4, anti-interleukin-31), substantiate the importance of itch in dermatology. We are delighted that, in this volume, we could bring together many of the key opinion leaders in the fields of basic and clinical “pruritology” to provide state-of-the-art reviews of the neuroanatomy and neurophysiology of peripheral and central itch. These articles are designed to help the practitioner understand the cellular and molecular basis of the itch that afflicts patients with various diseases, including atopic dermatitis and other inflammatory skin diseases, as well as systemic diseases, HIV, and cancer. We hope that this volume, which spans the basic and clinical science of pruritus, from bench to bedside, will give the reader greater insight into the pathogenesis of pruritus, and provides an approach for managing the itch patient in daily clinical practice.

Pruritus: Management Algorithms and Experimental Therapies

A.A. Marghoob, MD | Akihiko Ikoma, MD, PhD | Ferda Cevikbas, PhD | Martin Steinhoff, MD | Timothy G. Berger, MD

Pruritus (itch) is a major symptom in many dermatologic as well as systemic diseases and
has a dramatic impact on the quality of life in these patients. The symptom of itch has to be
treated on the basis of its pathophysiology and its underlying disease. In daily practice, a
“quick” diagnosis of the underlying disease is often difficult, although a rapid relief of the
itch is desired. We often treat patients on the basis of the symptomatology. A rational
therapeutic ladder for a symptomatic therapy is useful until the final diagnosis has been
confirmed. There are probably many subtypes of pruritus, just as there are many diseases
that cause itch. The pathophysiology in many subtypes of pruritus is still poorly understood,
hindering a rapid and targeted treatment strategy. An extensive diagnostic workup is often
required to determine the final cause(s) of the itch. Thus, in daily life, physicians often start
with a more or less rational therapeutic strategy to combat the debilitating itch. We present
possible therapeutic ladders that form the basis for effective therapeutic itch strategies in
various diseases. On the basis of our current knowledge about the different pathophysiologies
of itch, on clinical trials or case reports, and our own clinical experience, we aim to
present therapeutic ladders for the rapid as well as long-term management of itch. Finally,
we summarize current exciting developments of experimental strategies in itch research
and in clinical development for itch therapy.
Semin Cutan Med Surg 30:127-137 Published by Elsevier Inc.