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Abstract Pruritus is an unpleasant sensation leading to the desire to scratch. It is the most common
symptom in dermatology, and various skin and systemic diseases can be associated with the presence of
itching. Pruritus may also be provoked by numerous drugs. Although the exact epidemiologic data are
still absent, it is generally accepted that elderly people frequently suffer from pruritus, and the problem
of itching in this population remains a challenge for clinicians. The elderly often complain of numerous
comorbidities that complicate the determination of the cause of pruritus, as well as its treatment.
Physical and mental deprivation may complicate proper assessment of pruritus severity and negatively
impair compliance with complex antipruritic therapies. Taking also into account heterogeneity of
possible causes of pruritus, every patient with pruritus must be handled individually, regarding the
diagnostic procedures and antipruritic therapy.
2011 Elsevier Inc. All rights reserved.
Introduction
Pruritus is defined as an unpleasant sensation that may
lead to intensive scratching.1 It is the most common
symptom in dermatology, one that can occur with or without
concomitant visible skin changes. Pruritus may be considered as acute (lasting less than 6 weeks) or chronic (lasting
more than 6 weeks).1 It can be localized or generalized.
Various skin and systemic diseases have been characterized
as being associated with the presence of itching (Tables 1
and 2), and different mechanisms have been proposed to
explain its origin. We have summarized current knowledge
about the problem of itching in the elderly population, hoping
that we will encourage physicians and researchers to concen Corresponding author. Tel.: +48 71 327 0941.
E-mail address: jszepiet@derm.am.wroc.pl (J.C. Szepietowski).
0738-081X/$ see front matter 2011 Elsevier Inc. All rights reserved.
doi:10.1016/j.clindermatol.2010.07.002
Pruritus classification
A new, two-step classification of pruritus has recently
been proposed by the International Forum for the Study of
Itch (IFSI).1 The IFSI classification was based on two
previous classifications of itching2,3 but additionally included important aspects of our current understanding of pruritus.
The IFSI classification1 distinguishes three groups of pruritic
individuals: those having pruritus on diseased skin (group I),
pruritus on nondiseased skin (group II), and pruritus with
secondary skin scratch lesions (group III). It also specifies six
categories of underlying pruritogenic diseases: dermatologic,
systemic, neurologic, psychogenic, mixed, and other
16
Table 1
A. Reich et al.
Pruritic skin diseases occurring in the elderly
Table 2
pruritus
Liver diseases
Primary biliary cirrhosis
Primary sclerosing cholangitis
Extrahepatic cholestasis
Hepatitis B and C
Kidney diseases
Chronic kidney insufficiency
Hematologic diseases
Polycythemia vera
Hodgkin disease
Non-Hodgkin lymphomas
Leukemias
Myeloma multiplex
Iron deficiency
Systemic mastocytosis
Hypereosinophilic syndrome
Myelodysplastic syndromes
Endocrine disorders
Hyperthyroidism
Hypothyroidism
Hyperparathyroidism
Diabetes
Neurologic diseases (neuropathic pruritus)
Brain injury/tumor (frequently unilateral pruritus)
Sclerosis multiplex
Small fiber neuropathy
Solid tumors (paraneoplastic pruritus)
Carcinoid syndrome
Infectious diseases
HIV infection/AIDS
Infestations
Criteria
Definitions
Drug-induced pruritus
Owing to a high frequency of chronic diseases present in
the elderly population, older people often simultaneously
take a number of medicines. Many systemic and topical
drugs can induce pruritus.6 Although drug-induced pruritus
(pruritus without skin rash) is not a distinct category but
summarized under systemic origin according to the IFSI
classification, this adverse effect should be taken into
account when assessing patients with chronic itch. Frequently, the cause of itching is not a systemic or neurologic
disease, but rather the treatment that was initiated.
The most important drugs that might be responsible for
chronic pruritus have been listed in Table 4. The pathogenesis of drug-induced pruritus differs depending upon the
causative agent. Acute pruritus may be secondary to druginduced skin lesions; however, a number of other possible
mechanisms of drug-induced chronic pruritus have been
postulated, including cholestatic liver injury, xerosis of the
skin, deposits of a drug or its metabolites in the skin,
phototoxicity, or neurologic mechanisms. Frequently, the
underlying mechanism is unknown.6
Drug-induced pruritus may be localized or generalized
and can start with the first dose or may be delayed in time
for several weeks or even months.7-9 It may resolve
shortly after the drug is discontinued10 or may persist
even for several months or years after treatment withdrawal.11-13 A clear time-relation has been described for
some drugs, and interruption of the drug leads to cessation
of pruritus. Usually, pruritus lasts in this group less than 6
17
weeks, fulfilling the definition of acute pruritus. With other
drugs, pruritus lasts much longer due to the underlying
mechanisms; for example, in hydroxyl ethyl starch-induced
Table 4
Drug group
Antihypertensive drugs
Examples
Angiotensin-converting
enzyme inhibitors
Angiotensin II antagonists
(sartans)
-Adrenergic blockers
Calcium channel blockers
Methyldopa
Sildenafil
Antiarrhythmic drugs
Amiodarone
Anticoagulants
Ticlopidine
Fractionated heparins
Antidiabetic drugs
Biguanides
Sulfonylurea derivants
Hypolipemic drugs
Statins
Antibiotics and
Penicillins
chemotherapeutics
Cephalosporins
Macrolides
Carbapenems
Monobactams
Quinolones
Tetracyclines
Lincosamides
Streptogramin
Metronidazole
Rifampin
Thiamphenicol
Trimethoprim/
sulfamethoxazole
Antimalarials
Psychotropic drugs
Tricyclic antidepressants
Selective serotonin reuptake
inhibitors
Neuroleptics
Antiepileptics
Carbamazepine, fosphenytoin,
oxcarbazepine, phenytoin,
topiramate
Cytostatics
Chlorambucil
Paclitaxel
Tamoxifen
Cytokines, growth factors,
Granulocyte-macrophage
and monoclonal antibodies colony-stimulating factor
Interleukin 2
Matuzumab
Lapatinib
Plasma volume expanders
Hydroxyethyl starch
Others
Antithyroid agents
Nonsteroidal antiinflammatory
drugs
Corticosteroids
Sex hormones
Opioids
Xanthine oxidase inhibitors
a
18
pruritus, the symptom is induced by neuronal storage, which
is relieved after degradation of the substance. This can
be grouped as chronic pruritus because it lasts for more than
6 weeks.6
In addition, many drugs were described to induce chronic
pruritus by unknown mechanisms, presenting another group
of chronic drug-induced pruritus. Therapy is very difficult in
this group, including the decision to interrupt or change the
drug. According to our experience, interruption for at least
6 weeks is necessary to prove that chronic pruritus is due
to the accused drug.
A. Reich et al.
radiation, pollution, or nicotine.21-23 Aging skin is characterized by atrophy of the epidermis and dermis due to loss of
collagen, degeneration of the elastic fibre network, and loss
of hydration. Characteristic of aging is a progressive loss of
function and structural integrity resulting in impaired
immune response and skin barrier function, vascular
impairment, metabolic imbalance of reactive oxygen species,
and components of the extracellular matrix.24,25 Hence,
molecular mechanisms that protect and defend against
extrinsic factors decrease progressively over a lifetime.
Besides the natural aging of the skin, a higher rate of
comorbidity, decreased mobility, and drug-induced adverse
effects are additional reasons that elderly people are at higher
risk for skin-related as well as pruritic disorders.20,25
Clinically, aged skin is characterized by atrophy, wrinkling,
fragility, alterations in pigmentation, a higher frequency of
benign and malignant tumors, and a greater tendency to
xerosis.26,27 Altogether, these factors contribute to a greater
susceptibility to dermatologic diseases and pruritus.
Pruritus in elderly patients is frequently associated with
dry skin.15,20,28 Advanced forms of xerosis usually present as
asteatotic dermatitis with fine scaling due to the loss of
naturally moisturizing free fatty acids in the stratum
corneum.20,29 Superficial cracks and polygonally fissures
are characteristic for this skin condition, first described as
eczema craquel.20
Evaluation of pruritus
A very complex and heterogenous pathogenesis of
pruritus makes a determination of the cause of itching a
significant challenge for any physician treating patients with
pruritus. For that reason, every patient with itching has to be
considered individually because this symptom may be a
sign of many, completely different diseases with various
prognosis. The proper antipruritic therapy can be successful,
however, if the underlying cause is identified. Although the
reason of pruritus cannot be determined in some people
despite a thorough examination, the proper diagnostic
procedures can identify the underlying cause in most
pruritic individuals.30
Every patient with pruritus should undergo careful history
and full physical and dermatologic examination. A detailed
history of itching episodes should begin with inquiries into
onset, location, diurnal rhythm, and alleviating or aggravating factors surrounding an itching period.20 Abrupt onset of
itch is uncommon for systemic causes of pruritus and is more
frequently observed in drug reactions, infestations, and
contact dermatitis.15 Worsening of pruritus after showering
is typical for asteatotic dermatitis but may also be seen in
aquagenic pruritus accompanying polycythemia vera. An
increase of pruritus during the night is observed in nearly all
types of itch, but is especially characteristic for scabies. The
patient history should also include a detailed data about
19
decrease xerosis. Furthermore, localized pruritus may be
diminished with cold wet dressings. Keeping the nails short
in patients with severe pruritus may prevent excoriations and
other secondary scratch lesions.
Topical therapies
Cooling agents
Some substances, like menthol, may decrease the
intensity of itching due to evoking a cooling effect by
activation of low temperature receptors in the skin. The
major limitation of menthol usage is a short-term efficacy,
usually lasting for less than 30 minutes, and the potential
irritant property of this compound. Currently, a huge hope is
put on novel agents (eg, ilicin) that will produce a longlasting cooling effect on the skin.
Anaesthetics
Formulations based on benzocaine or lidocaine are the
most widely used among anesthetics. They may be useful in
localized pruritus, especially in neuropathic pruritus; however, they can induce allergic contact dermatitis and may
induce side effects in the circulatory system if applied too
frequently or used for a long time.33 Another compound with
weak anesthetic properties is 3% polidocanol. It has been
used in therapy for itching accompanying psoriasis, atopic
dermatitis, and other forms of dermatitis, and in uremic
pruritus.34,35
Antihistamines
Doxepin (5%) is effective in atopic and contact dermatitis
and in microbic dermatitis.36-38 The drug should be applied
to a maximum of 10% of body surface. The total daily dose
must not exceed 3 grams. The antipruritic effect is observed
about 15 minutes after application. Other topical antihistamines have limited efficacy and may induce contact allergy
and are therefore not preferable.
Capsaicin
Capsaicin owes its antipruritic properties by desensitization of sensory nerve fibers, thus interrupting the
conduction of cutaneous pruritus and burning pain. The
application of capsaicin is connected with burning sensations during the first days of usage. To prevent this
problem, a 0.025% capsaicin should be used initially, and
subsequently, the concentration can be slowly increased to
0.1%. Capsaicin has been shown effective in the treatment
of notalgia paraesthetica (localized pruritus in the scapular
region of the back), prurigo nodularis, and in uremic
pruritus.33,39,40
Corticosteroids
Topical corticosteroids have limited value in the treatment of pruritus. They might only be effective in inflammatory skin conditions by decreasing inflammation and,
secondarily, pruritus.2,33
20
Calcineurin inhibitors
Calcineurin inhibitors (pimecrolimus, tacrolimus) are
potent antipruritic drugs in patients with atopic dermatitis.
Although some initial reports also suggested their value in
other pruritic conditions, controlled studies did not confirm
these observations.41,42
Endocannabinoids
Endocannabinoids, such as anandamide or N-palmitoyl
ethanolamine, are promising new compounds that activate
cannabinoid receptors in the skin. In uncontrolled studies
they were in therapy for pruritus in atopic dermatitis, chronic
renal failure, prurigo nodularis, and in anal pruritus.43-46
Systemic therapies
Antihistaminics
Antihistaminics are the most widely used antipruritic
remedies and are the treatment of choice in the histaminedependent pruritus, such as urticaria or mastocytosis.47 The
newer drugs with low lipophilicity are recommended
because they have poor penetration into central nervous
system and less commonly produce side effects. The efficacy
of antihistaminics in other types of pruritus is questionable. If
they are needed, the first generation of antihistaminics is
usually administered because of their sedative properties,
which could be helpful in pruritic patients.2,33
Opioid receptor antagonists/agonists
The data on the pathogenesis of pruritus indicate that receptor agonists partake in the central mediation of
pruritus.9 This observation led to the use of the -receptor
antagonists naltrexone and naloxone in the treatment of
various types of recalcitrant pruritus. These agents were
successfully used in uremic pruritus, cholestatic pruritus,
prurigo nodularis, and in opioid-induced pruritus.9,48,49 The
treatment can be started with oral naltrexone monotherapy
(25-150 mg/d) or with intravenous naloxone (0.02 g/kg/
min), followed by oral naltrexone.
Activation of other opioid receptors, namely -receptors,
may also produce itching relief. Nalfurafine, a selective opioid receptor agonist, has been approved in Japan for the
treatment of uremic pruritus.50 Currently, this drug is also
being tested for other indications such as atopic dermatitis.
Ondansetron
Ondansetron is a serotonin receptor 3 (5-HT3) antagonist
that might be effective in opioid-induced pruritus.9,51 Some
data had indicated its potential advantage in cholestatic
pruritus, but controlled studies failed to confirm its efficacy.
Cholestyramine
Resins, such as cholestyramine, may be helpful in pruritus
related to cholestasis. The optimal dose is 12 grams;
however, the prolonged use of this drug may lead to
deficiency of lipid-soluble vitamins. The treatment is also
A. Reich et al.
frequently connected with nausea, flatulence, and constipation, which limit their wide usage.
Gabapentin and pregabalin
Gabapentin and pregabalin are antiepileptic agents that
decrease neuronal transmission. Both drugs were successfully used in neuropathic pruritus (postherpetic itch, brachioradial pruritus) and in severe pruritus of chronic renal failure,
cholestasis, and after burns. The initial dose of gabapentin is
300 mg/d and can be gradually (of about 300 mg every third
day) increased to the most effective dose (the maximum
is 2400 mg/d).52-55 Pregabalin is administered in the initial
dose of 50 to 75 mg and can be increased to 300 mg/d.
Antidepressants
Antipruritic effect may also be observed with antidepressant drugs, mainly serotonin reuptake inhibitors such as
paroxetine or fluvoxamine. Pruritus relief was noted in
polycythemia vera, paraneoplastic pruritus, cholestatic pruritus, and prurigo nodularis.56,57 Antidepressants are usually
recommended as a second- or third-line antipruritic therapy.
Aprepitant
Aprepitant is an oral neurokinin-1 receptor antagonist,
blocking the action of substance P and is approved for the
treatment of nausea and vomiting during cancer treatment.
A recent report indicates that aprepitant may be useful for
the treatment of chronic pruritus.58 Because the substance
is very expensive and controlled studies are missing,
aprepitant cannot be recommended for use in chronic
pruritus to date.
Other therapies
Phototherapy
UVB phototherapy is the treatment of choice in uremic
pruritus and may also be helpful in the therapy for cholestatic
pruritus and HIV-associated pruritus. UVB phototherapy
decreases the number of mast cells and free nerve endings in
the skin.59 Psoralen and ultraviolet A (PUVA) treatment may
also be useful, mainly in skin diseases with pruritus such as
psoriasis, atopic dermatitis, mycosis fungoides, or lichen
planus. PUVA was also effective in pruritus accompanying
polycythemia vera and in aquagenic pruritus.
Psychotherapy
Psychotherapy is helpful in the treatment of somatoform
pruritus. Psychotherapy was also used in patients with atopic
dermatitis (combat of stress-related itching episodes) or
neurotic excoriations.
Acupuncture
Acupuncture, both classic and electroacupuncture, may
bring some benefits for patients with pruritus. The efficacy of
acupuncture was proven in patients with uremic pruritus.60
21
Fig. 1
Fig. 2
The therapy for pruritus accompanying hematologic malignancies is shown in Figure 3. In patients with solid tumors,
the treatment of pruritus should be started with paroxetine or
mirtazapine, or both drugs together.
Pruritus in HIV-infected individuals is frequently related
to comorbidities, and the causative therapy should be
initiated first. If pruritus was assumed to be associated
specifically with HIV infection, indomethacin (25 mg/d)
may bring relief.2 Some benefit was also observed after
UVB phototherapy or thalidomide (100 mg/d). Localized
neuropathic itch may benefit from anesthetics or capsaicin;
in generalized itching due to neuronal damage, neuroleptics (eg, gabapentin, pregabalin, carbamazepine) should
be tried first.2,61
22
A. Reich et al.
Fig. 3
Conclusions
Elderly people often complain of pruritus that may be
induced by a number of dermatologic, systemic, or
neurologic diseases, or can be of psychogenic origin.
Numerous comorbidities found in older patients frequently
complicate the determination of the cause of pruritus and
also make the treatment very difficult. Furthermore, physical
and mental deprivation may complicate the proper assessment of pruritus severity and negatively impair the patient's
compliance with complex antipruritic therapies. Taking into
account all these aspects of pruritus and older age, it must be
underlined that every patient with senile pruritus must be
rigorously examined and treated individually regarding both
the diagnostic procedures and antipruritic therapy.
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