Tuesday, July 03, 2007
Chronic itch (pruritus) is a common complaint in many
inflammatory skin diseases, as well as in systemic diseases such as
chronic kidney failure, chronic liver disease, HIV, and lymphoma.
Chronic itch is defined as a prolonged itch that lasts more than 3
months. Chronic itch may continue when treatment stops, depending
on the origin and state of the symptom.1
A recent clinical classification for chronic pruritus has been
proposed by the International Forum for the Study of Itch (IFSI).
It is divided into three major groups:
- The first group encompasses patients with skin diseases
(pruritus on primary diseased skin). Acute secondary scratch
lesions may or may not be present, such as those that often occur
with excoriated atopic dermatitis, excoriated psoriasis, or
- Patients comprising the second group experience pruritus
without any skin lesions (pruritus on primary non-diseased skin).
Again, acute secondary scratch lesions may or may not be
- The third group of patients present with prominent, chronic
scratch lesions (eg, prurigo nodularis, lichen amyloidosis, or
lichen simplex) secondary to an underlying cause. The underlying
origin may be a systemic disease (eg, uremic pruritus) or a skin
disease that leads to massive scratch lesions.
Another well-known form of itch in chronic sufferers is
intractable pruritus,1 which is an itch that cannot be
treated in the generally accepted course of medical practice. It is
important to acknowledge that such patients are encountered weekly
in dermatology clinics and they do suffer. In such cases, a more
holistic approach is required by an interdisciplinary team, with
involvement of both patients and their families. It integrates
pharmacologic and non-pharmacologic treatment with needed
psychotherapy and rehabilitation.
Chronic itch induces a series of consistent physical and
psychological changes that can significantly impair patients'
quality of life such as difficulty sleeping, difficulty
concentrating, decreased sexual desire and sexual function,
agitation, and depression. In addition, eczematous lesions
resulting from scratching can become secondarily infected,
particularly in patients with atopic dermatitis. In the recent
international Dialysis Outcomes and Practice Patterns Study
(DOPPS), evaluating more than 18,000 patients on hemodialysis,
pruritus was associated with a 17% higher mortality risk, an effect
that was no longer significant after adjustment for measures of
sleep quality. Another large cross-sectional study in Oslo
consisting of 18,770 adult responders showed that more than 8% of
the population reported that they suffered from itch, which was the
most common cause of skin morbidity. Itch was also strongly
associated with reporting poor general health.2
Chronic Itch and Chronic Pain
Chronic itch has many similarities to chronic pain. Both are
unpleasant sensory experiences and consist of multidimensional
phenomena, including sensory discriminative, cognitive, evaluative,
affective, and motivational components. In most cases, chronic itch
and pain result from an interaction between the brain and
skin.3 Recent studies in patients with chronic itch
demonstrate that repetitive painful stimuli, such as electrical,
noxious heat pain, and scratching stimuli distal to an itchy
stimuli, may be perceived as itch. Sensitization of nerve endings
is a well-known mechanism of inflammatory pain. A similar mechanism
occurs in chronic itch. Central sensitization in chronic itch is
caused by sensitization of second-order neurons in the dorsal horn,
thereby leading to increased sensitivity to itch. This increased
sensitivity to itch is coined alloknesis (itchy skin) and can be
observed when touch- or brush-evoked itch occurs around an itching
site.4 This phenomenon is analogous to the
better-known allodynia. Alloknesis is a prominent feature of atopic
dermatitis3,5 and explains patients' complaints of
severe pruritus associated with sweating, sudden changes in
temperature, and dressing and undressing.
Sensitization of nerve endings is a well-known mechanism of
inflammatory pain. A similar mechanism occurs in chronic itch.
Central sensitization in chronic itch is caused by sensitization of
second-order neurons in the dorsal horn, thereby leading to
increased sensitivity to itch. This increased sensitivity to itch
is coined alloknesis (itchy skin) and can be observed when touch-
or brush-evoked itch occurs around an itching site.4
This phenomenon is analogous to the better known allodynia.
Alloknesis, is a prominent feature of atopic
dermatitis3,5and explains patients' complaints of severe
pruritus associated with sweating, sudden changes in temperature,
and dressing and undressing.
Based on our increased understanding in recent years of chronic
itch and its significant impact on patients' quality of life, it is
imperative to treat chronic itch as a disease in its own right
rather than a bothersome symptom similar to that proposed for
chronic pain by the European Federation of IASP (International
Association for the Study of Pain) Chapters.
The main goal in treating chronic itch is reduction of itch
intensity. Although there are no general-purpose antipruritic
drugs, recent findings of specific neural networks involved in itch
transmission have led to novel therapeutic targets. These include
inhibition of itch transmission in the central nervous system with
anticonvulsants, antidepressants, and selective serotonin reuptake
inhibitors (SSRI) as well as combined serotonin-norepinephrine
reuptake inhibitors (SNRI).6 In addition, gabapentin may
inhibit central itch pathways, as it does in pain. Several case
series and small-scale studies have shown gabapentin to be
effective in the treatment of itch, particularly neuropathic and
chronic kidney disease-associated pruritus. For more localized
chronic itch, topical agents that work directly at the site of
application include local anesthetics, substance P depletors, such
as capsaicin, and antinflammatories such as topical aspirin and
An imbalance of the endogenous opioidergic system has received
recent attention in terms of the pathophysiology of pruritus per
se, as well as in chronic pruritic conditions. Kappa agonists have
shown promising results in phase III studies for chronic kidney
disease-associated pruritus; however, they are as of yet not
available in the market.9 Butorphanol, which is a kappa
agonist and a mu antagonist, was reported to be an effective
treatment for patients with chronic, severe intractable pruritus
due to inflammatory skin and systemic diseases.10
Similar to chronic neuropathic pain, refractory cases of chronic
itch often require the use of two agents with synergistic
mechanisms of action.
Chronic itch is a major healthcare problem for millions of
patients worldwide and needs to be addressed as a disease state
rather than a mere symptom accompanying skin and systemic disease.
Adopting such an approach will yield better outcomes for millions
of itchy patients.
- Yosipovitch G, Greaves MW. Definitions of Itch. In: Yosipovitch
G, Greaves MW, Fleischer AB, et al, eds. Itch: basic mechanisms
and therapy. New York: Marcel Dekker; 2004:2.
- Dalgard F, Svensson A, Holm JO, et al. Self-reported skin
morbidity among adults: associations with quality of life and
general health in a Norwegian survey. J Investig Dermatol Symp
- Ikoma A, Steinhoff M, Stander S, et al. The neurobiology of
itch. Nat Rev Neurosci. 2006;7(7):535-47.
- Schmelz M. Complex interactions between pain and itch.
- Heyer G, Ulmer FJ, Schmitz J, et al. Histamine-induced itch and
alloknesis (itchy skin) in atopic eczema patients and controls.
Acta Derm Venereol. 1995;75(5):348-52.
- Summey BT Jr, Yosipovitch G. Pharmacologic advances in the
systemic treatment of itch. Dermatol Ther.
- Yosipovitch G. Pruritus: An Update. Current Problems in
- Yosipovitch G, Greaves MW, Schmelz M. Itch. Lancet.
- Wikstrom B, Gellert R, Ladefoged SD, et al. Kappa-opioid system
in uremic pruritus: multicenter, randomized, double-blind,
placebo-controlled clinical studies. J Am Soc Nephrol.
- Dawn AG, Yosipovitch G. Butorphanol for treatment of
intractable pruritus: a case series and review of the literature.
Submitted for publication 2005.