REVIEW

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Evaluation of chronic pruritus in

olderpatients
Sonja A Grundmann & Sonja Stnder
Chronic pruritus, one of the main symptoms in dermatologic diseases, is often intractable and has
a high impact on a patients quality of life. In addition to dermatologic disorders, chronic pruritus
is associated with systemic and neurologic, as well as psychologic, diseases. Aging skin is considered
to be more susceptible to pruritic disorders. Thus, owing to demographic changes, pruritus is
becoming more prevalent. The elderly are often afflicted with comorbidities and polypharmacy,
which can complicate diagnosis and therapy. In this review we present a rational work-up adapted
to the special premises and needs of geriatric patients. This may facilitate the choice of suitable
therapeutic regimens.

Advances in medicine and technology have grad-
ually led to increased life expectancy and aging
societies, particularly in industrial countries.
The elderly (those older than 65years of age),
represent the fastest growing segment of these
populations [13] . Hence, diseases that impact
the geriatric population are gaining more and
more importance owing to these demographic
changes. Although dermatological diseases
affect individuals of all ages, the likelihood of
developing skin-related disorders is increased
in the elderly [4] . Pruritus is one of the main
symptoms of dermatologic diseases that leads
to specialist consultations. In addition, pruritus
may have its origin in a variety of dermatologic,
systemic, neurologic, as well as psychologic,
conditions [57] . However, the origin of pruritus
often remains unclear and appropriate concise
diagnosis and care of pruritus is challenging.
Frequency of chronic pruritus
Owing to the fact that people are living longer,
diseases of the skin will become more preva-
lent, as will pruritus. However, although it
has often been described as the most frequent
symptom in dermatologic diseases and general
medicine, only limited epidemiological data are
available. According to a cross-sectional study
in Oslo, Norway, pruritus affects 8.4% of the
general population; while in a large French
study, 42% of patients with skin diseases stated
that they had experienced pruritus [5,8] . In a
German pilot study, a lifetime prevalence of
22.6% was recorded [9] . Our own data dem-
onstrate a prevalence of 17% among German
employees (Blome, Augustin, Stnder, Unpublished
Data) . Although gender differences have not
been greatly explored, a higher level of pru-
ritus among females has been reported [9,10] .
Conducted with a focus on elderly people, only
a small number of difficult-to-match studies
have investigated prevalence and incidence of
chronic pruritus [6] . According to a Turkish
study involving 4099 elderly dermatological
patients, 11.5% reported pruritus, and the
highest prevalence was recorded in patients
older than 85years [11] . In a Thai study involv-
ing 149elderly patients, pruritic diseases were
the most common at 41% [12] . In our own
study population, 48.3% of patients with pru-
ritus were aged 60years and older (Stnder etal.,
Unpublished Data) . However, with regard to the
elderly population, more epidemiological inves-
tigations are needed in order to analyze age-
specific aspects. For this purpose, the use of an
accepted international classification of pruritus
is essential.
Pruritus definition & classification
Pruritus is an unpleasant sensory perception that
causes an intense desire to scratch and has a high
Author for correspondence
Neurodermatology & Competence
impact on quality of life [1315] . Although the
Center Pruritus, Department of
more acute forms are regularly part of the inborn Dermatology, University of
alert system against certain noxious stimuli such Mnster, Von-Esmarch-Strasse 58,
as parasites, chronic pruritus, defined as lasting D-48149 Mnster, Germany
longer than 6weeks, has to be considered to be Tel.: +49 251 835 6501
predominantly pathologic [16] . The intensity of Fax: +49 251 835 2559
pruritus ranges from mild to severe and can have sonja.staender@uni-muenster.de
a high psychosocial impact, affecting patients
daily activities and sleep [1719] . The symptom Keywords
is subjective, encountered as either isolated or
aged dermatitis geriatric
accompanying a skin disease or sometimes as itch prurigo pruritus skin
a leading symptom of extracutaneous diseases aging therapy
(e.g.,malignancies, metabolic disorders, drug
reactions or infections) [2023] . The quality,
intensity and diurnal rhythm of itch are impor- part of
tant clinical characteristics, although they
currently have limited diagnostic value.

10.2217/AHE.09.84 2010 Future Medicine Ltd Aging Health (2010) 6(1), 5366 ISSN 1745-509X 53
REVIEW Grundmann & Stnder

Several classifications have been published that
consider these different etiologies and clinical
morphologies [2426] . The International Forum
for the Study of Itch (IFSI) has proposed a clas-
sification that considers clinical as well as differ-
ential diagnostic factors. First (I), pruritus on pri-
mary diseased, inflamed skin as in inflammatory
and infectious diseases, autoimmune disorders,
lymphomas or drug reactions; second (II), pru-
ritus on primary nondiseased, noninflamed skin
as in neurologic or psychiatric origin; and third
(III), secondary scratch lesions, which includes
patients with excoriations, crusts, papules, nod-
ules and chronic secondary scratch lesions such
as prurigo nodularis. However, the presence or
absence of skin changes does not allow the deter-
mination of the origin. Thus, for differential
diagnostic purposes, a categorization of under-
lying pruritogenic diseases has been proposed
including dermatological, systemic, neurological
and psychiatric/psychosomatic diseases. Patients
with more than one underlying disease should
be categorized as mixed. If no underlying dis-
ease can be identified, pruritus should be class
ified as pruritus of undetermined origin (PUO)
(Table1)[16] .
Pathophysiology of aged skin
Skin aging results from a combination of chrono
logical and environmental factors. It involves
intrinsic, hormonal, biological and genetic fac-
tors as well as extrinsic, noxious stimuli such as
life-long accumulation of UV radiation, pollution
or nicotine [2729] . Aging skin is characterized by
atrophy of the epidermis and dermis, owing to loss
of collagen, degeneration in the elastic fiber net-
work and loss of hydration. Characteristic of both
intrinsic and extrinsic aging is a progressive loss
of function, structural integrity and physiological
functions of the skin, which involve an impaired

Table 1. Etiologies of chronic pruritus in geriatric patients.

Origin Examples
Dermatological
Inflammatory Xerosis, drug reactions, atopic dermatitis, psoriasis and contact dermatitis, scars
Infectious Mycotic, bacterial and viral infections and folliculitis, scabies, pediculosis, arthropod
reactions and insect bites
Autoimmune Bullous dermatoses, bullous pemphigoid and dermatomyositis
Neoplasms Cutaneous Tcell lymphoma (especially erythrodermic variants), cutaneous Bcell lymphoma
and leukemic infiltrates of the skin
Systemic
Endocrine and metabolic Chronic renal failure, diabetes mellitus, liver diseases with or without cholestasis and
hyper/hypothyroidism and malabsorption
Infectious Herpes zoster, helminthosis, parasitosis and HIV
Hematological and lymphoproliferative Iron deficiency, polycythaemia vera, Hodgkins disease, non-Hodgkin lymphoma,
plasmocytoma, visceral neoplasms, solid malignoma, carcinoid syndrome, hemochromatosis
and multiple myeloma
Drug induced Opioids, angiotensin-converting enzyme inhibitors, amiodarone, hydrochlorothiazid,
estrogens, simvastatin, hydroxyethyl starch and allopurinol
Neurological
Neurogenic (without neuronal damage) Only a few clinical examples are available at present, potentially hepatic itch with increased
endogenous m-opioids (that reduce itch)
Neuropathic (neuronal damage causes itch) Cerebral or spinal infarcts, small fibre neuropathy, neoplasms, abscesses, brachioradial
pruritus, notalgia paresthetica, postherpetic neuralgia, vulvodynia and multiple sclerosis
Psychiatric/psychosomatic
Somatoform pruritus Depression, psychosis, mania, somatoform disorders, obsessive or compulsive disorder,
anxiety tactile hallucinosis and fatigue
Mixed
Combination of pruritic disorders Combination (e.g.,of diabetes mellitus, renal failure and xerosis in one patient)
Unknown
Pruritus of undetermined origin

54 www.futuremedicine.com future science group


immune response and skin barrier function, vas-
culature atrophy, metabolic imbalance of reactive
oxygen species and components of the extracellular
matrix [4,30] . Hence, molecular mechanisms
that protect and defend against extrinsic factors
decrease progressively over a lifetime. As people
age, these skin structure changes and a gradual
loss of cell function leads to more sensitive skin
that is prone to diseases. Beyond normal aging of
the skin, a higher rate of comorbidity, decreased
mobility and drug-induced side effects are among
the reasons that the elderly are at higher risk for
skin-related as well as pruritic disorders [31,32] .
Clinically, aged skin is characterized by atrophy,
wrinkling, fragility, alterations in pigmentation,
and a higher frequency of benign and malignant
tumors,
as well as a greater tendency towards xero-
sis [33,34] . Altogether, these factors contribute to a
greater susceptibility to dermatologic diseases, as
well as to pruritic symptoms either of dermatologic
or systemic origin.
Pruritic dermatological diseases
in the elderly
As mentioned previously, senescence of the skin
is an aggravating as well as a triggering fac-
tor for certain skin diseases, although most of
them, such as atopic dermatitis or psoriasis, can
be observed across all ages. Asteatotic eczema is
one of the most common dermatological disor-
ders in the elderly, and is often associated with
pruritus. It usually presents as an advanced
form of xerosis with fine scaling owing to the
loss of naturally moisturizing free fatty acids
in the stratum corneum [35] . Superficial cracks
and polygonally fissures are characteristic of
this dermatosis, first described as eczema
craquel [36] . Seasonal prominent dehydration
explains why elderly individuals with astea-
totic eczema classically present with pruritic
and dry skin on the pretibial area during the
winter months. Further eczematous dermatitis
commonly observed in the elderly include num-
mular eczema and stasis dermatitis. Nummular
eczema presents as pruritic, coin-shaped lesions
that are most commonly found on the extremi-
ties, trunk and the dorsum of the hands. For
differential diagnostic reasons, stasis dermatitis
should be considered, which has a strong prefer-
ence for the lower extremities owing to chronic
venous insufficiency. Mild-to-moderate forms
of itch and burning may even occur before skin
signs are present [37] .
Aging of the skin immunological system may
explain why autoimmune skin disorders are
more common in the elderly [38] . In particular,
future science group
Evaluation of chronic pruritus in olderpatients Review
bullous dermatoses are associated with high
morbidity and mortality. Bullous pemphigoid
is the most prevalent autoimmune blister-
ing disease in geriatric patients, which usually
appears as multiple blisters on the extremities
and the lower abdomen. It has to be considered
that tumor-associated autoimmune dermatoses
such as pemphigus or dermatomyositis are more
common in the elderly and have a poorer prog-
nosis. Furthermore, bullous pemphigoid may be
triggered by furosomide, angiotensin-converting
enzyme inhibitors, penicillin and antipsychotic
drugs [3941] . Pemphigus vulgaris may also
accompany severe pruritus for weeks or months
before the onset of blistering; however, this is
observed more commonly in bullous pemphi-
goid. Beyond those autoimmunological disor-
ders, erythroderma is a severe dermatosis that is
more common in the elderly. Erythroderma is an
intense widespread reddening of the skin owing
to a variety of causes. The most common cause
is an exacerbation of a pre-existing skin disorder,
such as psoriasis, atopic dermatitis, contact der-
matitis and cutaneous Tcell lymphoma, as well
as being a very common adverse drug reaction.
It may also be a symptom or sign of a systemic
disease such as solid or hematological malignan-
cies, graft-versus-host disease or infections[42,43] .
Thus, many HIV-positive people are first seen
by clinicians due to pruritus. HIV is often not
considered a disease of elderly because few indi-
viduals are routinely tested and, therefore, the
prevalence is underestimated. However, over
10% of all new AIDS cases in the USA occur in
those over the age of 50years. [44] . Furthermore,
scabies has to be considered in cases with an
intense nocturnal itch [15,45,46] . Resident patients
of nursing homes and extended care facilities
are at a high risk of developing scabies owing to
facilitated transmission and delayed diagnosis.
Scabies is known as an imitator of other pruritic
dermatologic diseases (e.g., atopic dermatitis).
In addition to the underlying disease, a gen-
eralized, and sometimes severe, chronic pruritus
may occur, which often persists in spite of suc-
cessful therapy of the underlying skin disorder.
Thus, every dermatologic pruritic disorder can
be associated with secondary skin lesions includ-
ing discrete superficial excoriation, erosions,
ulcers, thickened hyperpigmented nodules or
hypopigmented atrophic scars (Figure1) .
Pruritic systemic diseases in elderly
Pruritus without any primary skin changes can
often be the initial, as well as the key, symptom
of a variety of systemic diseases. Uremia, liver
Aging Health (2010) 6(1) 55
REVIEW Grundmann & Stnder
Figure 1. 72year old male with prurigo papulosa for 1year due to a
multifactorial origin of pruritus. Histological examination could rule out
bullouspemphigoid.
and hematological diseases, as well as malignan-
cies and lymphomas, are among the diseases that
can cause pruritus (Table1) .
Ureamic pruritus is a common complica-
tion of end-stage renal disease, affecting a
third of dialysis patients and mainly developing
23months after dialysis is initiated, but it may
also develop before dialysis [4749] . Triggering
factors may include uremia-related abnormali-
ties (particularly those involving calcium, phos-
phorus and parathyroid hormone metabolism,
and accumulation of uremic toxins) [5052] .
Pruritus is either generalized or localized, espe-
cially on the back, head, abdomen and arms,
Table 2. Drugs that could induce or sustain pruritus.
Category Examples
Analgetics Opiods and nonsteroidal anti-inflammatory drugs
Antibiotics Penicillin, cephalosporins, macrolids, carbapenems, monobactams, tetracycline and others
Anticoagulants Ticlopidine and fractionated heparins
Antidiabetics Biguanids and sulphonylurea derivates
Antiepileptics Carbamazepine, phenytoin and others
Antimalarials Chloroquin
Cardiovascular drugs Diuretics, angiotensin-converting enzyme inhibitors, angiotensin-II antagonists (sartans), b-adrenergic
blockers, calcium-channel blockers, amiodarone and statins
Cytokines Granulocytemacrophage colony stimulating factor, IL-2 and others
Cytostatics Tamoxifen, paclitaxel and others
Plasma volume expander Hydroxyethyl starch
Psychotropics Tricyclic antidepressants, selective serotonin-reuptake inhibitors and neuroleptics
Uricostatic/ uricosuric agents Allopurinol, colchizin and probenecid
56 www.futuremedicine.com
and worsens at night [53] . Specific skin lesions
are not observed, and secondary pruritic lesions
such as excoriation, prurigo or lichenifications
are common in the course of pruritus over a long
time. Furthermore, predominantly intrahepatic
cholestatic diseases, such as the autoimmuno-
logical primary biliary cirrhosis, are often symp-
tomatic with pruritus [54,55] . Patients often report
the most intensive itch being in the palms of the
hands and soles of the feet, but it may also be
generalized. Bile salt, progesterone metabolism,
histamine and endogenous opiods in cholesta-
sis have been proposed to induce pruritus [56,57] .
Diabetes mellitus is the most common endocrine
disease and is accompanied by dermatological
diseases and cutaneous manifestations in up to
70% of patients. Epidemiologic data concern-
ing the frequency of pruritus in patients with
diabetes mellitus are inconsistent and prevalence
ranges from 2.7 to 49% [5860] . Beyond meta-
bolic triggering factors, complications such as
neuropathy or impaired wound healing may
contribute to the susceptibility for chronic itch.
Other pruritic conditions are the result of poly-
pharmacy, targeting predominantly chronic dis-
eases of advanced age (Table2) . Pruritus usually
presents with symptoms of the systemic disease
but it has occasionally been reported to precede
these symptoms by years. Chronic pruritus is
known to be an early symptom in Hodgkins dis-
ease or polycythaemia vera, appearing in advance
of any other disease manifestations [61] . In any
case, the demographic situation increases the
possibility of pruritus being associated with solid
or hematological malignancies [62] . Beyond that,
pruritus may accompany known psychological
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 Evaluation of chronic pruritus in olderpatients Review

abnormalities [63,64] . This fact should be consid-
ered owing to a high prevalence of, for example,
depression and anxiety in geriatric patients [65] .
Polyneuropathia and residua of cerebrovascular
events are also highly prevalent in the elderly
population and can evoke variants of neuro-
pathic itch [66] . Especially in older patients, more
than one underlying disease may contribute to
the itch (multifactorial pruritus) [6] . However,
the cause of pruritus can sometimes be easily
established, but in many cases the underlying
origin remains unknown (i.e., in cases of PUO).
Diagnostics
Patients with chronic pruritus may present with
a broad variety of symptoms; and diagnostic
management is challenging. Before starting any
therapy, a substantial history should be obtained
and a thorough physical examination should be
performed followed by laboratory investigation
testing complete blood count, erythrocyte sedi-
mentation rate, and renal, liver and thyroid func-
tion (Table3) . A full physical and dermatologic
examination should be conducted in order to
survey for excoriations, ulcerations, erythema,
scars and any evidence of infections or parasit-
osis, in order to discover any underlying disease
that may be causing chronic pruritus. A detailed
history of the excoriation episodes should begin
with inquiries into the onset, location, diurnal
rhythm and alleviating or aggravating factors
surrounding an excoriation period. A visual ana-
log scale is the most commonly used method to
assess itch intensity. The patient indicates the
intensity of pruritus on a scale with extremes
from 0: no pruritus at all to 10: the worst
pruritus you can imagine [67] . This method can
easily be automated, allowing the analysis of a
day profile [68] and can also be easily assessed in
geriatric patients with cognitive problems.
Therapy: principles & guidelines
Pruritus management is challenging because
many therapies fail. Owing to the fact that
chronic pruritus is a complex, multifactorial
phenomenon, no generally accepted theory for
its management exists, and many circumstances
prevent optimal treatment. The treatment regi-
mens of dermatologic disorders of the aged patient
are often less than optimal, because the special
needs and limitations of this population are not
adequately considered. The elderly often com-
plain of numerous comorbidities that complicate
therapeutic attempts. Therefore, pharmacological

Table 3. Stepwise graduated diagnostic assessment of patients with chronic pruritus.

Spectrum of Rational diagnostic approach
diagnostic assessment
History
Medical history, onset and course of pruritus, presence and onset of skin lesions, known systemic and
dermatological diseases and allergies, predisposition for atopic dermatitis, drug intake and family history
Clinical examination
Basic Physical and skin examination by a dermatologist
In-depth Internal, neurologic, psychosomatic and gynecologic/urologic consultation
Laboratory investigation
Basic Electrolytes, erythrocyte sedimentation rate, blood count, differential blood count, total protein, protein
electrophoresis, iron metabolism, level of folic acid, zinc and vitamin B12, blood glucose, uric acid, urea,
creatinine, liver transaminases, bilirubin, alcalic phosphatase, hepatitis serology, thyreoid function test,
antibodies against the thyroid gland, parathyreoid hormone level, total IgE serum level, prostate-specific
antigen, urine status and fecal-occult blood test
In-depth Antimitochondrial antibody, immunoglobins, indirect immunofluorescence, parathormon, porphyrine and
bone marrow investigation
Diagnostic procedures
Skin biopsy (histology and direct immunofluorescence) in case of presence of skin lesions that could not have
been classified upon clinical criteria, and performance of an additional skin biopsy, Helicobactor pylori,
13
C urea breath test, lactose deficiency H2-exhalation test and endoscopy/biopsy
Imaging
Basic Chest x-ray and abdomen ultrasound
In-depth Computed tomography or MRI scan especially for tumor detection and, in case of neuropathic pruritus,
lymph-node ultrasound

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space is limited. The skin condition also needs to
be closely monitored owing to its state and age-
related fragility [69] . Furthermore, physical and, at
times, mental limitations hinder compliance with
complex therapies. Owing to the huge variety of
systemic origins of pruritus, a successful therapeu-
tic regimen includes a thorough screening for any
underlying disease. An individualized approach,
which combines systemic and topical therapy, is
necessary. Depending on the underlying cause,
causal therapies range from the specific treatment
of a primary dermatological disorder, avoidance of
contact allergens, discontinuation of a medication
and specific internal, neurological and psychiatric
therapies, to the surgical therapy of neoplasms. A
targeted therapy of the underlying disease often
results in relevant relief of pruritus (e.g., dur-
ing/after chemotherapy in Hodgkins disease)
although many patients need additive antipruritic
therapies. Beyond this, superinfected dermatoses
or secondary scratch lesions may require anti-
infectants and antimicrobiotic therapy. However,
immediate relief of pruritus has to be an initial
treatment goal.
camphor creams [72] or local anesthetic-contain-
ing creams such as polidocanol can temporarily
reduce pruritus. Patients can apply these therap
ies as necessary, particularly during pruritic
exacerbation or in cases of nocturnal pruritus. If
pruritus still persists, a combined or consecutive
step-by-step, symptomatic treatment is neces-
sary (Table4) . Therefore, symptom- and etiology-
related therapies as well as additional topical and
systemic therapies have to be utilized.
An appropriate topical therapy is essential for
successful treatment of different forms of pruri-
tus [73,74] . The patients individual requirements
(e.g.,the body region to be treated and the state
of the patients skin, including underlying der-
matosis) have to be considered. Hence, a suit-
able vehicle (e.g.,lotion, gel, cream or ointment)
should be chosen. Although this topical therapy
is essential in almost all geriatric patients com-
plaining of chronic pruritus, there is a high rate
of incompliance. Immobility and physical limit
ations in the elderly complicate effective topical
care of all affected skin areas, especially if the
therapy has to be applied more than once-daily.

Topical therapy Topical corticosteroids

Importantly, triggers and harmful regimens
such as alcoholic compresses or irritating tinc-
tures must be avoided. An appropriate fast-act-
ing approach to relieve acute pruritus attacks
includes moisturizing with lotions and other
lubricants (e.g., occlusive oily emollients or
humectants such as urea), which can help with
xerosis that often aggravates the pruritic condi-
tion [70,71] . In addition, cooling with menthol or
Topical corticosteroids may provide fast relief,
even of severe pruritus, in steroid-responsive
dermatosis. However, there are few studies that
provide evidence of a significant antipruritic
effect in the treatment of pruritus of differing
etiology [75] . If pruritus is one symptom among
others to suggest an underlying inflammatory dis-
order, topical glucocorticosteroids with a favor-
able side effect profile (e.g.,fluticasonpropionate,

Table 4. Step-by-step measures to relieve pruritus.

Step Measure taken
I General therapeutic measures:
Avoidance of skin dryness and irritating substances;
Moisturizing of the skin with hydrating skincare products adjusted to the individual skin condition;
Adequate, soft and loose-fitting clothes (e.g.,made of cotton, no wool and no synthetic materials);
Short-term pruritus relief: avoidance of scratching, application of creams/lotions containing urea, camphor, menthol,
polidocanol or tannic acid, moist or cooling compresses, cool showers and black tea compresses
Diagnosis of the underlying disease and etiologic therapy
Initial symptomatic therapy: oral antihistamines (alone or in combination), topical glucocorticosteroids
II Symptomatic and etiologic therapy (see main text)
III Symptomatic topical and/or systemic therapy (e.g.,capsaicin, calcineurin inhibitors, cannabinoid agonists,
montelukast, naltrexone, gabapentin or UVtherapy)
In the most severe cases: systemic glucocorticosteroids, immunosuppressants (cyclosporine A)
Accompanying therapy during each step
In cases of sleep disorders: sedating antihistamines, tranquilizers, tricyclic antidepressants or neuroleptics
Psychosomatic care and behavioral therapy
In cases of erosive scratch lesions: disinfecting substances and local glucocorticosteroids
Steps 13 can be administered additively (e.g.,antihistamines and ketotifen and calcineurin inhibitors in cases of renal pruritus) or consecutively.

58 www.futuremedicine.com future science group


ethylprednisolonaceponate or mometasonfuroate)
are helpful but are not sufficient to completely
abolish pruritus [76] . Nevertheless, increased skin
fragility and petechia can be induced by the pro-
longed use of topical steroids, especially in aged
skin. Therefore, a single application of topical
glucocorticosteroids for treating the symptom
of pruritus is not advised, although they can be
effectively applied in cases of secondary pruritic
scratch lesions.
Capsaicin
The active ingredient of chili peppers, the vanil-
loid-alkaloid capsaicin, owes its antipruritic prop-
erties to the desensitization of the sensory nerve
fiber and it interrupts the conduction of cutane-
ous pruritus and burning pain. It directly affects
polymodal nerve fibers (full ligand at the TRPV1
receptor), and is also effective in nonhistamine-
induced pruritus. Therefore, topically applied
capsaicin has been reported to be effective in
postherpetic neuralgia, notalgia paresthetica and
brachioradial pruritus, psoralen-ultraviolet A itch
and pain, aquagenic pruritus and prurigo nodula-
ris [77,78] . In cases of pruritus associated with der-
matoses, as well as on primarily noninflammatory
skin, the effect of capsaicin generally starts within
days. Capsaicin needs to be applied several times
daily (three to six times/day), which limits its use
in generalized pruritus, especially for physically
or mentally limited geriatric patients. It is impor-
tant to start this therapy gradually, increasing the
concentration (from between 0.025and0.05% to
between 0.075and0.1%) in order to attenuate
the initial neurogenic inflammation and burning
or pruritus.
Topical calcineurin inhibitors
The topical calcineurin inhibitors pimecrolimus
and tacrolimus were initially developed for the
treatment of atopic dermatitis. In addition to
the relief of skin lesions, a very good antipruritic
effect of topical calcineurin inhibitors has been
observed. Comparable with capsaicin, an initial
burning and pruritus may occur, which may give
clinical evidence of assumed TRPV1 binding. At
present, pimecrolimus (Elidel cream, Novartis)
and tacrolimus (Protopic ointment, Astellas,
Tokyo, Japan) have been proven to be effective for
other pruritic dermatoses, such as chronic irritant
hand eczema, steroid-induced rosacea, chronic
steroid-refractory graft-versus-host disease,
prurigo nodularis, lichen sclerosus and atrophi-
cus, genital psoriasis and scrotal eczema [7981] .
Owing to their more favorable side effect pro-
file, compared with topical corticosteroids,
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Evaluation of chronic pruritus in olderpatients Review
calcineurin inhibitors can be recommended for
the treatment of inflammatory dermatosis in the
elderly; however, long-term therapy is associated
with high costs.
Cannabinoid receptor agonists
Endogenous as well as synthetic cannabinoids are
known for their analgesic potency upon systemic
administration. Both cannabinoid receptors, CB1
and CB2, were found to be present on cutaneous
sensory nerve fibers [82] , which suggests a rational
basis for the use of cannabinoid receptor agonists
as topical therapy. Their activation by cutane-
ous application of a cannabinoid agonist could
significantly suppress experimentally induced
pain and itch sensation and erythema [83,84] .
Several papers have reported on a case series
where a cream containing a low concentra-
tion of N-palmitoylethanolamin (Physiogel AI
Cream/Lotion, Stiefel Laboratorium, Germany)
was applied, which relieved pruritus due to hemo-
dialysis [82] , atopic dermatitis[85] , PUO, and pru-
ritus in prurigo nodularis and lichen simplex [86] .
In the first application study the formula showed a
very good antipruritic effect in 63.6% of patients
without any relevant side effects; pruritus could
be reduced by 86.4%[86] . Recently, similar results
have been obtained in facial postherpetic neural-
gia [87] . However, N-palmitoylethanolamin has
recently been confirmed to elicit its antipruritic
capacity via non-CB1/CB2 receptors. Regarding
these upcoming targets, it may be speculated that
creams with another concentration or another
type of cannabinoid will have analogic or even
higher antipruritic properties.
Systemic therapy
When choosing a therapy, a step-by-step approach
depending on the severity of pruritus, expected
side effects and the general condition of the patient
should be considered. Systemic therapies should
be initiated if topical therapy or compliance fails.
Antihistamines/mast cell stabilizers
Most of the known pruritus mediators are mast
cell and histamine liberators. Antihistamines
have been the only available antipruritic ther-
apy for various types of pruritus. They must
be shown to be very effective when the itch
sensation is mediated by histamine, such as in
urticaria [88] . In chronic pruritus of any ori-
gin, antihistamines are of limited efficacy in
low dosage. Studies have detected antipruritic
effects of antihistamines (e.g.,terfenadine [89] or
azelastine [90,91]) in uremic pruritus while anti-
histamines such as cetirizine have demonstrated
Aging Health (2010) 6(1) 59
REVIEW Grundmann & Stnder
no efficacy in uremic pruritus [92,93] . Beyond
their antihistaminic effects, antihistamines
modulate immunological responses, such as
mediator release, adhesion molecule expression,
cytokines, chemokines and cell recruitment.
Accordingly, it could be shown that azelastine
had a clearly antipruritic effect by blocking
leukotriene B4 and substanceP [94] . However,
a recent case series suggests that a high dosage
or a combination of antihistamines have good
antipruritic effects in patients with dermatosis
and patients with PUO [95] . In elderly patients,
side effects of this high or multidosing have to
be carefully observed. Some studies point to an
antipruritic efficacy of mast cell stabilizers such
as ketotifen [96,97] .
Systemic corticosteroids
In spite of much clinical experience in inflamma-
tory skin disorders, there are no controlled stud-
ies investigating the efficacy of single systemic
glucocorticosteroids in pruritus. According
to clinical experiences, pruritus ameliorates
within a short time after intravenous adminis-
tration of glucocorticosteroids when treating,
for example, urticaria or drug-induced exan-
thema. In addition, in cases of severe allergic
contact dermatitis, exacerbated atopic derma-
titis and autoimmune diseases, such as bullous
pemphigoid, pruritus ceases quickly, which can
be explained by the high anti-inflammatory
potency of glucocorticosteroids. Therapy using
systemic glucocorticosteroids as an antipruritic
should not be considered for long-term treat-
ment considering its side effects; however, short-
term corticosteroid therapy can be used to bridge
treatment in patients with severe pruritus who
are changing to another therapy.
Leukotriene receptor antagonist
In chronic urticaria, a better reduction of pru-
ritus is achieved with a combination of the
leukotriene antagonist montelukast and cetiri
zine [98] or deloratadine [99] compared with
single antihistamine use alone. Zafirlukast
and zileuton have been described to have anti-
pruritic efficiacy in atopic dermatitis; however,
study results concerning the use of leukotriene
re ceptor antagonists in atopic dermatitis are
inconsistent [100103] .
Cyclosporin A
Cyclosporin A is known for its potent immuno
supressive effects. As well as being used in trans-
plant medicine or rheumatology, it is also used
in severe dermatosis such as psoriasis, atopic
60 www.futuremedicine.com
dermatitis and pyoderma gangrenosum [104] .
It has also been reported to have a significant
antipruritic effect in prurigo nodularis [105] ,
whereas the antipruritic mechanism is assumed
to be symptomatic owing to the anti-inflam-
matory effects of cyclosporine A [106] . However,
cyclosporine A has several side effects such as
nephrotoxicity, drug interactions and increasing
blood pressure, which limits its use, especially
in the elderly.
UV phototherapy
Many clinical studies demonstrate the efficacy
of different UV therapy regimes in dermatoses
associated with pruritus. However, to the best
of our knowledge, there have been no stud-
ies on chronic pruritus that do not relate to
the underlying dermatosis. The modulation
of anti-inflammatory and immunosuppressive
factors as well as antiproliferative effects and
mast cell apoptosis [107] can be assumed to
be significant factors of a UVinduced anti-
pruritic effect in inflammatory dermatoses.
Interestingly, the antipruritic effect has to be
mediated via systemic mechanisms [108110] .
In uremic pruritus in particular, the anti-
pruritic efficacy of UVB-therapy has been
reported[108,109,111] . There are further positive
reports regarding UVB-irradiation in the treat-
ment of the following diseases: pruritus asso-
ciated with polycythaemia vera (narrow-band
UVB) [112] , Hodgkins disease [113] and general-
ized pruritus [114] . Psoralen UVA therapy has
been reported to be successful in prurigo nodu-
laris and aquagenic pruritus for the duration of
therapy [115117] , although controlled studies
are lacking. Owing to its positive antipruritic
effects, UV phototherapy could be a rational
therapy for elderly patients.
Current concepts of pruritic pathways involve
peripheral nerve fibers and central nervous
structures, which play a central role in pruritic
sensory perception. Pruritus-specific receptors
have been observed; however, pain afferences
may communicate and interact with pruritus
neurons [106,118] . Together, these results have
encouraged the introduction of centrally acting
antipruritic substances.
Anticonvulsants & pain modulators
Anticonvulsants and pain modulators, such as
gabapentin or pregabalin, are known to modu-
late various receptor sides of dopamine, sereto-
nin and noradrenaline metabolism. Gabapentin
and pregabalin are used for neuropathic pain
and also have antipruritic effects [119121] . The
future science group

exact antipruritic mechanism is unknown, but
gabapentin has been demonstrated to be effec-
tive, particularly in the treatment of neuro
pathic pruritus such as brachioradial pruri-
tus[122] . Furthermore, a significant efficacy has
been reported in uremic pruritus [123] . Both
gabapentin and pregabalin, which is structurally
related to gabapentin, have to be titrated up to
an effective dose starting with a low initial dose
(initial dosage of gabapentin:100300mg/day;
maximum start dosage: up to 600mg/day; ini-
tial dosage of pregabalin:2575mg; maximum
start dosage:150mg) [80] . In the elderly, lower
dosages are sufficient. Side effects may occur,
especially in the elderly, including dizzines,
peripheral edema, worsening of diabetes mell
itus, which besides renal impairment may limit
use in the elderly.
Opioid receptor agonist/antagonists
Opiate use is associated with the appearance of
pruritus, and as a result m-opioid antagonists
have been tested for their antipruritic capacity.
Several clinical trials have proven a positive effect
of opioid receptor antagonists in different pru-
ritic dermatoses such as asteatotic dermatitis or
bullous pemphigoid. Double-blind, controlled
studies of cholestatic pruritus demonstrated a
significant decrease of pruritus after the applica-
tion of naloxone [124] , and nalmefene [125127] , as
well as naltrexone [128] . Naltrexone (Nemexin,
DuPont Pharma, one to two times/day) has the
advantage of oral application. In a large case
series with pruritus of different origins, 64.7%
of patients confirmed a good antipruritic effect
of naltrexon [129] . Studies focusing on renal pru-
ritus have reported contradictory results [130,131] .
Side effects such as nausea, vomiting, dizziness
and tiredness are reported during the first days
of therapy with opioid antagonists, which may
require inpatient care, especially in the elderly
with impaired mobility. Furthermore, thera-
peutic costs are high, so opioid antagonists are
mainly used as a second-line therapy.
Nalfurafine binds selectively to k-opioid
receptors and is synthesized as an analgesic.
It inhibits substance-P and histamine-induced
scratching and has been demonstrated in a
clinical study to significantly reduce uremic
pruritus [132] . Currently, the use of nalfurafine
is limited to clinical trials.
Antidepressants
Antidepressants directly influence central pru-
ritus perception. Tricyclic and tetracyclic anti
depressants and selective serotonin reuptake
future science group
Evaluation of chronic pruritus in olderpatients Review
inhibitors have been reported to have beneficial
effects; however, the exact antipruritic mechanism
is unknown.
Amitryptylin has been reported to be use-
ful in some cases of neuropathic pruritus.
The initial dose is 10mg three times daily or
25mg once-daily at bedtime. Another tricyclic
antidepressant, doxepin, shares amitryptylins
antipruritic, antihistaminic, antidepressant
and sedating properties. Therefore, it has been
used particularly for psychogenic and neuro-
pathic types of pruritus [133] . Doses range from
25to150mg at bedtime. Typically, 68weeks
of therapy are needed before results can be
seen. Mirtazapine is a tetracyclic antidepressant
with antihistaminic and serotonin-antagonistic
effects [134] . Doses of 15mg have been used suc-
cessfully in cholestatic, uremic, neuropathic and
paraneoplastic pruritus [135] ; higher doses do not
seem to be of any additional benefit and cause
more side effects. Nowadays, modern drugs,
such as selective serotonin reuptake inhibitors,
are available that have similar effects but a better
safety profile. Paroxetine (dose:20mg/day) was
reported to have a very good antipruritic effect
in patients with polycythemia vera, psychogenic
and paraneoplastic pruritus, as well as in pruri-
tus of nondermatologic origin [136138] . A recent
study confirmed that paroxetine and fluvoxa
mine have beneficial effects in different types of
pruritus [139] . As severe cardiac and central ner-
vous side effects such as drowsiness, vertigo and
fatigue have been described with paroxetine and
fluvoxamine use, especially in elderly patients,
this therapy should be used with caution until
ongoing studies have beencompleted.
Psychosomatic therapy
Beyond somatic therapy, psychosomatic thera-
pies (e.g.,behavioural therapy) have to be initi-
ated in time to break the vicious circle of itching
and scratching [140] . Patients with prurigo nodu-
laris in particular demonstrate an unconscious
automatic scratching behavior. Counseling with
a psychotherapist may be important for disorders
of mood and personality or in dealing with social
tensions. In patients with a coexisting depression,
psychotherapy in combination with a psycho-
pharmacologic therapy can be helpful to treat
pruritus [64] .
Conclusion & future perspective
Chronic pruritus remains a challenging diag-
nostic and therapeutic condition, especially in
elderly patients. Taking a patients medical history
may be more difficult and patients often already
Aging Health (2010) 6(1) 61
REVIEW Grundmann & Stnder

have a set of other medical or social problems
that accompany the pruritic disorder. In addi-
tion, due to skin aging, primary skin disorders
may have an altered appearance and comorbidi-
ties and drug therapy can complicate an accurate
diagnostic work-up. Therefore, an understand-
ing of the clinic al and pathophysiologic fea-
tures and a stepwise diagnostic and therapeutic
regimen considering the premises and needs of
the elderly is essential for therapeutic success.
Despite improvements in our understanding of
the pathophysiological mechanisms underlying
chronic pruritus states and the identification of
multiple pruritic mechanisms, the clinical need
for pharmacotherapies that are effective, nontoxic
and devoid of severe side effects remains predomi-
nant, especially for the growing elderly popula-
tion. Additional controlled studies that focus on
the elderly and reflect the broad variety of origins
and therapeutic options must be conducted.

Executive summary
Introduction
The elderly (>65years of age) are the fastest growing segment of the population.
Diseases that affect the geriatric population are gaining importance.
Pruritus is one of the main symptoms of dermatologic diseases.
Pruritus may also have its origin in a variety of systemic, neurologic and psychologic conditions.
Frequency of chronic pruritus
Although pruritus is the most frequent symptom in dermatologic diseases and in general medicine, there are only limited
epidemiological dataavailable.
Chronic pruritus most frequently occurs in elderly patients.
Pruritus definition & classification
Pruritus is an unpleasant sensory perception that causes an intense desire to scratch, with chronic pruritus defined as lasting longer
than 6weeks.
Several classifications have been published that take into account these different etiologies and clinical morphologies.
The International Forum for the Study of Itch has proposed a classification that considers clinical as well as differential
diagnosticreasons.
Pathophysiology of aged skin
Atrophy of the dermis (loss of collagen, degeneration in the elastic fiber network and loss of hydration) is related to intrinsic and
extrinsic aging.
Pruritic dermatological diseases in the elderly
Asteatotic eczema is one of the most common dermatological disorders in the elderly.
Aging of the skins immunological system may explain why autoimmune skin disorders are more common in the elderly, especially
bullous dermatoses.
Erythroderma is most commonly an exacerbation of a pre-existing skin disorder such as psoriasis, atopic dermatitis, contact dermatitis,
cutaneous Tcell lymphoma and malignancy, as well as adverse drug reactions.
Pruritic systemic diseases in the elderly
Beyond dermatologic diseases, pruritus without any primary skin changes can often be the initial, as well as the key symptom of a
variety of systemic diseases (e.g., uremia, liver and hematological diseases, as well as malignancies and lymphomas).
Diagnostics
Patients may present with a variety of symptoms and diagnostic management is challenging.
A good history, thorough physical examination and laboratory investigation should be performed before starting any therapy.
In order to assess itch intensity, a visual analog scale is the most commonly used assessment.
Therapy: principles & guideline
Chronic pruritus is a complex, multifactorial phenomenon.
No generally accepted measurement concept exists, and many circumstances prevent optimal treatment, especially in the elderly.
An individualized approach, which combines systemic and topical therapy, is necessary.
Topical therapeutics (e.g., steroids, capsaicin, calcineurin inhibitors and cannabinoid agonists) and systemical therapeutic options
(e.g., antihistamines/mast cell stabilizers, systemic steroids,leukotriene receptor antagonist, cyclosporin A , UV phototherapy,
anticonvulsives, opioid receptor antagonists and antidepressants) are reviewed in this article.
Conclusion
A rational work-up adapted to the special premises and needs of geriatric patients facilitates the choice of suitable
therapeuticregimens.

62 www.futuremedicine.com future science group


Financial & competing interests disclosure
The authors have no relevant affiliations or financial
involvement with any organization or entity with a finan-
cial interest in or financial conflict with the subject matter
or materials discussed in the manuscript. This includes
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Affiliations
Sonja A Grundmann
Neurodermatology & Competence Center
Pruritus, Department of Dermatology,
University of Mnster, Germany
Tel.: +49 251 835 6542
Fax: +49 251 835 8534
sonja.grundmann@ukmuenster.de
Prof. Dr Sonja Stnder
Neurodermatology & Competence Center
Pruritus, Department of Dermatology,
University of Mnster, Germany
Tel.: +49 251 8356 501
Fax: +49 251 8352 559
sonja.staender@uni-muenster.de
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