Pruritus

Published on 18/03/2015 by admin

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Pruritus

Amit Garg and Jeffrey D. Bernhard

Evidence Levels:  A Double-blind study  B Clinical trial ≥ 20 subjects  C Clinical trial < 20 subjects  D Series ≥ 5 subjects  E Anecdotal case reports

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Pruritus is a cutaneous sensation (usually unpleasant) that evokes an urge to scratch, rub, pick, and, in extreme cases, mutilate the skin in an attempt to obtain relief. We use the terms itch and pruritus interchangeably. Itch occurs as a characteristic feature of many skin diseases, such as atopic dermatitis and lichen planus. It can also occur as an unusual symptom of systemic disorders, such as hyperthyroidism, cholestasis, and uremia. Pruritus in the absence of a detectable rash, whether localized or generalized, poses both a diagnostic and a therapeutic challenge to even the most seasoned dermatologist. New findings in the neurophysiology of itch have led to specific therapies that target particular pathways and receptors in the nervous system.

Management strategy

Management of pruritus is directed toward its cause, which may not always be apparent, regardless of whether dermatitis is present. Many dermatoses itch, and it is beyond the scope of this chapter to discuss them all. Xerosis and scabies deserve special mention because both can have subtle findings with intensity of pruritus out of proportion to rash. In xerosis, an adequate skin care regimen and emollients are indispensable. One of the more common and embarrassing errors is to miss the diagnosis of scabies, and consideration of this diagnosis may avoid delays in treatment and undue suffering.

Failure to diagnose a primary skin disease does not rule out the possibility that one is present; time, repeated observation, and laboratory tests such as a skin biopsy may be required. When no rash is present, or when a rash is present but cannot be diagnosed, further evaluation is indicated. The evaluation should include a thorough medical history and physical examination, complete with a precise medication review and review of systems. The physical examination should include palpation for organomegaly and lymphadenopathy. The examiner should not be misled by non-specific secondary changes caused by rubbing, scratching, or secondary infection. A ‘peculiar’ eczematous dermatitis resistant to treatment may be a secondary phenomenon, not necessarily the primary diagnosis. Laboratory investigations are often essential in the clinical assessment of chronic pruritus, whether a rash is present or not. The presence or absence of constitutional signs or symptoms should be determined at the initial and follow-up visits.

The most serious error is to miss the diagnosis of an underlying systemic disease associated with pruritus. Some of the many systemic diseases that may cause pruritus include hematologic and solid malignancies, lymphoproliferative disorders, HIV, thyroid disease, iron deficiency, renal disease, hepatobiliary disease, connective tissue disease, neurologic disease, and drug hypersensitivity. Interval re-evaluation for associated systemic disease should be undertaken since pruritus may precede the diagnosis of a systemic disease by many months (as in primary biliary cirrhosis).

Specific investigations

For symptomatic relief, general skin hygiene measures (e.g., moisturization) and elimination of exacerbating factors (e.g., excessively dry air) are worthwhile but rarely sufficient. Tepid water baths using fragrance-free moisturizing soaps, emollients, unscented bath oils applied liberally after bathing, a cool moisture rich environment, and loose fit clothing are helpful. In the management of pruritus that does not respond to simple measures, treatment should be individualized based on etiology, severity, and regard for safety.

Neuropathic itch

Neuropathic itch arises as a consequence of pathology at one or more points along the afferent (sensory) pathway of the peripheral or central nervous system. Brachioradial pruritus (BRP) and notalgia paresthetica (NP) are the two best examples of the isolated sensory peripheral neuropathies seen by dermatologists. Workers in this field believe that dorsal spinal nerve radiculopathy, usually secondary to degenerative disease of cervical and thoracic vertebral bodies, lead to persistent itching, paresthesia, hypesthesia, or burning/stinging pain. The involved areas may also be hyperpigmented and excoriated. These forms of localized pruritus may go undiagnosed for quite some time. By the time patients fail to respond to various treatments and obtain a dermatology referral, the itch has often been going on for months and may have become generalized, with secondary changes that may be mistaken for a primary dermatosis. Several investigators have observed patients in whom brachioradial pruritus appears to have triggered generalization to areas beyond those normally involved in classic BRP.

Repeated application of capsaicin cream, which depletes axonal stores of substance P, may be an effective approach to the treatment of localized areas of neuropathic pain or itch. While evidence for the use of gabapentin in the treatment of BRP and NP is mostly anecdotal to date, it is being used increasingly with success for more widespread or otherwise recalcitrant neuropathic dysethesias, including itch and pain. Doses as high as 2400 mg or more daily in divided doses, as tolerated, may be necessary. Pregabalin, an analog of gabapentin, has also been effective in the treatment of neuropathic pain syndromes (such as post-herpetic neuralgia and diabetic neuropathy); there is evidence that it may be effective in treating neuropathic itch as well (e.g., BRP and post-herpetic pruritus).

First-line therapies

image Capsaicin A

Second-line therapies

image Gabapentin or pregabalin D

Cholestatic itch

Cholestasis, a reduction of bile flow, results from a variety of hepatic, as well as extrahepatic, diseases. While the pathophysiological link between cholestasis and pruritus is not fully understood, an increasing body of evidence supports the proposition that it occurs as a consequence of increased levels of endogenous opioids. Pruritus of cholestasis is typically widespread, characteristically involves the palms and soles, and may be accompanied by jaundice. Therapeutic interventions have focused on the removal of presumed pruritogens from the circulation (through the use of ursodeoxycholic acid, cholestyramine), induction of hepatic enzymes (rifampin), antagonism of endogenous opioid receptors (naltrexone, nalaxone, nalmefene), modulation of serotonin neurotransmission (sertraline), activation of cannabinoid receptors (dronabinol), and clearing water soluble and protein bound pruritogens through albumin-based dialysis (Molecular Adsorbent Recycling System, Prometheus®). Ultraviolet B (UVB) phototherapy and parenteral lidocaine are further therapeutic considerations.

First-line therapies

image Rifampin A
image Natrexone, nalmefene, naloxone A

Second-line therapies

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