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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

image Cholestyramine A
image Ursodeoxycholic acid A
image Sertraline A

The potent bile acid sequestrant colesevelam is not effective in cholestatic pruritus: results of a double-blind, randomized, placebo-controlled trial.

Kuiper EM, van Erpecum KJ, Beuers U, Hansen BE, Thio HB, de Man RA, et al. Hepatology 2010; 52: 1334–40.

In this randomized, double-blind, multicenter trial, 35 patients with cholestatic pruritus received 1875 mg of colesevelam, an anion-exchange resin with a sevenfold higher bile acid-binding capacity than cholestyramine, or an identical placebo twice daily for 3 weeks. Despite significantly lower mean serum bile acid levels in the colesevelam treated group, there was no significant difference between groups with respect to the following: percent of patients with ≥40% reduction in pruritus VAS scores, quality-of-life scores, and severity of cutaneous scratch lesions.

Third-line therapies

image Albumin-based dialysis E
image Ultraviolet B phototherapy E
image Parenteral lidocaine A
image Dronabinol E

Itch associated with cholestasis of pregnancy

First-line therapies

image Ursodeoxycholic acid A

Second-line therapies

image S-adenosyl-L-methionine B
image Cholestyramine B

Renal itch

Patients with renal itch tend to have dry skin, have increased numbers of dermal mast cells, and may have a variety of unidentified circulating pruritogens, possibly including opioid peptides. Pruritus associated with chronic renal failure is usually an unremitting generalized itch which is more common among hemodialysis patients. Some patients experience itch localized to the shunt arm of dialysis patients. Presence or intensity of pruritus does not correlate with blood urea or creatinine levels. The condition is difficult to manage and the only reliably effective treatment remains to be kidney transplant. Fortunately, incidence of uremic pruritus is decreasing as dialysis membranes with improved biocompatibility are being used. Optimizing general skin care measures with emollients to reduce xerosis should be a fundamental part of the treatment plan. Antihistamines are generally not helpful for uremic pruritus. However, the tricyclic antihistamine doxepin, whose use in renal itch is not described in the literature, may be helpful because of its sedating and antidepressant properties. While UVB phototherapy is the mainstay of treatment, gabapentin and naltrexone have also shown efficacy in trials. A number of other less conventional therapeutic interventions have reported success.

First-line therapies

image Emollients with high water content A
image Narrowband UVB phototherapy B
image Broadband UVB phototherapy B
image Gabapentin A
image Pregabalin B
image Naltrexone A
image Nalfurafine hydrochloride B

Narrowband ultraviolet B phototherapy for patients with refractory uraemic pruritus: a randomized controlled trial.

Ko MJ, Yang JY, Wu HY, Hu FC, Chen SI, Tsai PJ, et al. Br J Dermatol 2011; 165: 633–9.

In this single-blind, randomized, controlled trial, patients with refractory uremic pruritus were randomized to receive NB-UVB phototherapy or time matched long-wave UVA radiation as a control. NB-UVB was given three times per week for 6 weeks. The dose of NB-UVB started at 210 mJ/cm2 and was increased by 10% for each treatment. Both NB-UVB and control groups had significant and comparable improvement in the pruritus intensity VAS scores during phototherapy and follow-up. Compared with the control group, the NB-UVB group showed a significant improvement in the affected body surface area (p=0.006), but not in sleep quality. The authors concluded that NB-UVB phototherapy does not show a significant effect in reducing pruritus intensity compared with a control group for refractory uremic pruritus.

Second-line therapies

image Zinc sulfate A
image Capsaicin 0.03% cream A
image Acupuncture: Quchi (LI11) acupoint A
image Homeopathic treatment with verum A

Third-line therapies

image Cholestyramine A
image Activated charcoal D
image Thalidomide B
image Parathyroidectomy B

Itch associated with malignancy

Pruritus associated with malignancy is a common occurrence among patients with lymphomas and advanced malignancy. It may be one of the most bothersome symptoms to a cancer patient and its management is challenging. The best evidence to date in the treatment of pruritus associated with malignancy exists for paroxetine.

Second-line therapies

image Mirtazapine E
image Butorphanol E

Itch associated with hematologic disorders

Pruritus associated with hematologic diseases, e.g., polycythemia vera and myelodysplastic syndrome, is often severe and intractable to the limited therapies available. Phototherapy remains the primary line of therapy for these patients.

First-line therapies

image Narrowband UVB phototherapy D
image Psoralen photochemotherapy D

Miscellaneous diseases associated with itch

Miscellaneous diseases associated with itch include psychogenic pruritus, HIV, hydroxyethyl starch-deposition-induced pruritus, and essential pruritus of the elderly (Willan’s itch).

Of interest for symptomatic treatment

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