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Bolognia: Dermatology, 2nd ed.

SECTION TWO PRURITUS

Chapter 6 Cutaneous NeurophysiologyGil 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 responsiblemediators 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 andmotivational 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

A-beta (A) Large + >30 m/s Light touch

Moving stimuli

A-delta (A) Small + 230 m/s Pain (nociceptors)

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PRIMARY AFFERENT NEURONS THAT INNERVATE THE SKIN

Fiber Diameter Myelination Conduction velocity Respond to

Thermal

Mechanical

Chemical, including pruritogens

C Small

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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 non-

specific 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 morespecific 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.

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