Bolognia: Dermatology, 2nd ed.

SECTION TWO PRURITUS

Chapter 6 Cutaneous Neurophysiology

Gil Yosipovitch, Aerlyn G Dawn, Malcolm Greaves Key features A distinct subset of nociceptive C neurons has been identified that specifically transmits the sensation of itch Itch mediators act both peripherally (e.g. histamine, proteases) and centrally (e.g. opioids) via several mechanisms There is overlap between chronic itch and chronic pain, including activation of multiple brain areas and associated neuromediators (e.g. nerve growth factor and neurotrophin 4) Significant cross-talk between cutaneous nerve fibers and the stratum corneum is a possible mechanism for pruritus associated with impaired barrier function (e.g. xerosis, atopic dermatitis) No specific antipruritic treatment is available; however, combination therapies that reduce itch sensitization and topically acting drugs that counteract the responsible mediators are promising treatment strategies

INTRODUCTION
The skin is a sensory organ with a dense network of highly specialized afferent sensory nerves and efferent autonomic nerve branches. Nerve fibers are found at all levels of the skin and transmit sensations including temperature, touch, vibration, pressure, itch and pain (Table 6.1). Neuropeptides (e.g. nerve growth factor, substance P) are secreted from these nerve fibers and several exert immunologic effects. Itch (syn. pruritus) is the dominant symptom of skin disease; almost all inflammatory skin diseases can have associated pruritus. Itch is a multidimensional phenomenon with sensory discriminative, cognitive, evaluative and motivational components. In most instances, itch results from interactions that involve the brainskin axis.

Table 6.1 -- Primary afferent neurons that innervate the skin. PRIMARY AFFERENT NEURONS THAT INNERVATE THE SKIN Fiber Diameter Myelination Conduction velocity Respond to + + >30 m/s 230 m/s Light touch Moving stimuli A-delta (A) Small Pain (nociceptors) A-beta (A) Large

PRIMARY AFFERENT NEURONS THAT INNERVATE THE SKIN Fiber Diameter Myelination Conduction velocity Respond to Thermal Mechanical Chemical, including pruritogens C Small <2 m/s Pain (nociceptors) Itch (histamine- sensitive)[*] Thermal[*] Mechanical
*

Separate C fibers (5% of total C nerve fibers) carry both pruritogenic and thermal stimuli, but not mechanical stimuli.

Pruritus has many similarities to pain. Both are unpleasant sensory experiences, but the behavioral response patterns differpain elicits a reflex withdrawal, whereas itch leads to a scratch reflex. Nonetheless, both can lead to serious impairment of quality of life. Despite being a common complaint[1] and being so rudimentary that almost every two- or four-footed creature experiences it, medical science is still struggling to understand the mechanisms of itch and how best to inhibit the sensation. The connection between itch and scratching is so close that in some languages the same word refers to both itch and scratch. Itch is restricted to the skin, tracheal mucous membrane, and several mucocutaneous junctions (e.g. conjunctivae). Interestingly, the nerves in the deeper layer of the reticular dermis and subcutaneous fat do not seem to transmit itch. Pruritus is often perceived by the patient as the most unendurable symptom of his or her disease. It is also a feature of many systemic diseases and may be the initial or presenting symptom. Copyright 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

Chapter 7 Pruritus and Dysesthesia

Elke Weisshaar, Alan B Fleischer Jr, Jeffrey D Bernhard Synonyms: Notalgia paresthetica: subscapular pruritus, posterior pigmented pruritic patch, hereditary localized pruritus Brachioradial pruritus: solar pruritus, solar pruritus of the elbow, brachioradial summer pruritus Prurigo nodularis: chronic circumscribed nodular lichenification (Pautrier) Aquagenic pruritus: bath pruritus Key features

Pruritus is the most common complaint of patients with dermatologic disease Pruritus can occur with or without skin lesions, and may represent dermatologic or systemic disorders Pruritus is a symptom of various complex pathogenic mechanisms that cannot be attributed to one specific cause or disease Pruritus should challenge the dermatologist to search for any underlying etiology Management of pruritus can often be achieved by implementing specific and nonspecific treatments

INTRODUCTION
Pruritus can be defined subjectively as a poorly localized, non-adapting, usually unpleasant sensation which elicits a desire to scratch. The biologic purpose of pruritus is to provoke scratching in order to remove a pruritogen, a response likely to have originated when most pruritogens were parasites. Pruritus is the most common dermatologic symptom. It can arise from a primary cutaneous disorder but may also be a symptom of an underlying systemic disease in an estimated 10% to 50% of patients[1]. Diagnoses to consider include metabolic disorders, hematologic disease, malignancy, HIV infection, a complication of pharmacologic therapy, and neuropsychiatric disorders (see Ch. 8). In some patients, pruritus can occur in the absence of visible skin signs. To date, there is no definitive classification system for pruritus, based on either clinical features or pathophysiology, but a possible scheme has recently been proposed[2,3,3a]. While the limited understanding of the pathogenesis of pruritus has hampered the development of adequate therapies, as reviewed in Chapter 6, recent discoveries provide hope for more specific therapies in the future[4]. When a patient complains of pruritus, there is a rational way to assemble the myriad of etiologies into finite groups, to evaluate the patient in a thoughtful manner, and then to correct the underlying cause (if possible) and treat the pruritus with currently available therapies. Copyright 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com