PRURITUS/ITCH: THE SCIENCE AND TREATMENT

Jun
2011
Vol. 30. No. 2

Introduction

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.
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Anatomy and Neurophysiology of Pruritus

Akihiko Ikoma, MD, PhD | Cordula Kempkes, PhD | Ferda Cevikbas, PhD | Martin Steinhoff, MD

Itch has been described for many years as an unpleasant sensation that evokes the urgent desire to scratch. Studies of the neurobiology, neurophysiology, and cellular biology of itch have gradually been clarifying the mechanism of itch both peripherally and centrally. The discussion has been focused on which nerves and neuroreceptors play major roles in itch induction. The “intensity theory” hypothesizes that signal transduction on the same nerves leads to either pain (high intensity) or itch (low intensity), depending on the signal intensity. The “labeled-line coding theory” hypothesizes the complete separation of pain and itch pathways. Itch sensitization must also be considered in discussions of itch. This review highlights anatomical and functional properties of itch pathways and their relation to understanding itch perception and pruritic diseases. Semin Cutan Med Surg 30:64-70 © 2011 Elsevier Inc. All rights reserved.

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Management of Itch in Atopic Dermatitis

Joerg Buddenkotte, PhD | Judith Hong, MD | Martin Steinhoff, MD | Timothy G. Berger, MD

Atopic dermatitis is a common, pruritic, inflammatory skin disorder. Chronic, localized, or
even generalized pruritus is the diagnostic hallmark of atopic dermatitis, and its management
remains a challenge for physicians. The threshold for itch and alloknesis is markedly
reduced in these patients, and infections can promote exacerbation and thereby increase
the itch. Modern management consists of anti-inflammatory, occasionally antiseptic, as
well as antipruritic therapies to address the epidermal barrier as well as immunomodulation
or infection. Mild forms of atopic dermatitis may be controlled with topical therapies, but
moderate-to-severe forms often require a combination of systemic treatments consisting of
antipruritic and immunosuppressive drugs, phototherapy, and topical compounds. In addition,
patient education and a therapeutic regimen to help the patient cope with the itch and
eczema are important adjuvant strategies for optimized long-term management. This review
highlights various topical, systemic, and complementary and alternative therapies, as well
as provide a therapeutic ladder for optimized long-term control of itch in atopic dermatitis.
Semin Cutan Med Surg 30:71-86 © 2011 Elsevier Inc. All rights reserved.

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Neuropathic Itch

Anne Louise Oaklander, MD, PhD

Chronic itch can be caused by dysfunctions of itch-sensing neurons that produce sensory
hallucinations of pruritogenic stimuli. The cellular and molecular mechanisms are still
unknown. All neurological disease categories have been implicated, and neurological
causes should be considered for patients with otherwise-unexplained itch. The same
neurological illnesses that cause neuropathic pain can also or instead cause itch. These
include shingles (particularly of the head or neck), small-fiber polyneuropathies, radiculopathies
(eg, notalgia paresthetica and brachioradial pruritis), and diverse lesions of the
trigeminal nerve, root, and central tracts. Central nervous system lesions affecting sensory
pathways, including strokes, multiple sclerosis, and cavernous hemangiomas, can cause
central itch. Neuropathic itch is a potent trigger of reflex and volitional scratching although
this provides only fleeting relief. Rare patients whose lesion causes sensory loss as well as
neuropathic itch can scratch deeply enough to cause painless self-injury. The most common
location is on the face (trigeminal trophic syndrome). Treating neuropathic itch is
difficult; antihistamines, corticosteroids, and most pain medications are largely ineffective.
Current treatment recommendations include local or systemic administration of inhibitors
of neuronal excitability (especially local anesthetics) and barriers to reduce scratching.
Semin Cutan Med Surg 30:87-92 © 2011 Elsevier Inc. All rights reserved.

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The Itch of Liver Disease

Nora V. Bergasa, MD

Itch is a complication of liver disease. It is hypothesized that this type of itch is mediated,
at least in part, by increased central opioidergic tone; a peripheral component may coexist.
The role of serotonin, bile acids, substance P, and lipophosphatidic acid and the activity of
the enzyme that generates it, autotoxin, has been proposed in the pathogenesis of itch.
Scratching activity was significantly suppressed in association with the placebo tablet in a
controlled, double-blind study; this finding supports the exploration of the placebo effect on
the itch sensation and the inclusion of behavioral methodology in clinical trials in patients
with this complication of liver disease.
Semin Cutan Med Surg 30:93-98 © 2011 Elsevier Inc. All rights reserved.

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