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Chronic Pruritus in the Elderly:


Pathophysiology, Diagnosis and Management
Article in Drugs & Aging February 2015
DOI: 10.1007/s40266-015-0246-0 Source: PubMed

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Rodrigo Valdes Rodriguez
Temple University
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Drugs Aging (2015) 32:201215


DOI 10.1007/s40266-015-0246-0

REVIEW ARTICLE

Chronic Pruritus in the Elderly: Pathophysiology, Diagnosis


and Management
Rodrigo Valdes-Rodriguez Carolyn Stull
Gil Yosipovitch

Published online: 19 February 2015


Springer International Publishing Switzerland 2015

Abstract Chronic itch in the elderly is a common problem, with a significant impact on quality of life and sleep in
elderly patients. Chronic itch may be attributable to several
causes, including dry skin, immunosenescence and neural
degeneration. Itch may also be caused by skin diseases,
such as seborrhoeic dermatitis and stasis dermatitis; systemic conditions, such as end-stage renal disease and diabetes; and psychogenic conditions, such as depression and
anxiety. The use of polypharmacy may also cause itch,
with or without a rash. Specifically, thiazides and calcium
channel blockers have been known to cause itch in elderly
patients. Management should be tailored according to the
underlying dermatological or systemic aetiology of itch.
Topical treatment is the mainstay of therapy, providing
special emphasis on skin hydration and barrier repair. In
addition, topical and oral medications that target the nervous system and reduce neuronal hypersensitization, such
as gabapentin and selective antidepressants, have a role in
treating patients with severe chronic itch. Furthermore,
management must account for changes in metabolism and

pharmacokinetics of drugs in the aging population in order


to prevent the occurrence of adverse effects.

Key Points
Chronic itch in the elderly is a common problem,
with a significant impact on quality of life and sleep.
Common causes are skin dryness, immunosenescence
and neuropathy.
Topical treatments include moisturizers, anti-inflammatories, and local anaesthetics.
Systemic treatments include antihistamines, antidepressants (selective serotonin reuptake inhibitors and
selective norepinephrine reuptake inhibitors) and
neuroactive drugs.

1 Introduction

R. Valdes-Rodriguez  C. Stull  G. Yosipovitch (&)


Department of Dermatology and Itch Center, Temple University
School of Medicine, 3322 North Broad Street, Medical Office
Building, Suite 212, Philadelphia, PA 19140, USA
e-mail: gil.yosipovitch@tuhs.temple.edu

Chronic itch is a very common and debilitating problem in


the geriatric population [1]. Multiple causes of itch in the
elderly have been reported [2, 3]. It is important to better
understand how aging relates to chronic itch in order to
provide geriatric patients with preventative strategies and
optimal treatments [4]. This review focuses on the related
pathophysiological mechanisms, diagnoses and treatment
options for elderly patients suffering from chronic itch. A
systematic literature search, using Medline and PubMed,
limited to the English language, was performed using the
major search terms pruritus, elderly itch, geriatric itch,
immunosenescence, skin aging and xerosis itch.

202

R. Valdes-Rodriguez et al.

2 Epidemiology

3.1 Dry Aging Skin (Xerosis)

The elderly population (above 60 years of age) is expected


to double in size from 2010 to 2050 [57]. Itch is one of the
most common complaints among elderly patients in dermatology clinics worldwide, with a reported prevalence
ranging from 7.3 to 37.5 % [813]. In a recent comprehensive study using a standardized itch questionnaire administered to geriatric outpatient and nursing home
patients, the prevalence of chronic itch was reported to be
25 %, with high itch intensity [visual analogue scale (VAS)
score 6 2.1] [1].

Xerosis is considered to be the most common cause of itch


in elderly patients, with a prevalence ranging from 38 to
85 % [12, 1416]. In a study done by the authors, xerosis
was present in 69 % of patients with chronic itch, compared with only 19 % of patients without itch [1]. Multiple
skin changes in the elderly have been related to xerosis: (1)
alterations in the barrier function of the stratum corneum
(SC), including cellular and intercellular lipid matrix
(ILM) changes; (2) pH variations; (3) alterations in SC
proteases; (4) decreased activity of sebaceous and sweat
glands; and (5) decreased oestrogen levels. All of these
factors may contribute to itch induction [17].
The SC is the most superficial layer of the epidermis.
The SC functions as a barrier to prevent transepidermal
water loss and also provides protection from external
hazards [18, 19]. The SC constantly undergoes cellular
turnover [20]. As skin ages, the normal process of
desquamation can be altered, leading to the appearance of
dry skin [20, 21]. A casecontrol study comparing elderly
subjects who had generalized pruritus and xerosis with ageand sex-matched healthy controls found that subjects with

3 Pathophysiology
Chronic itch in the elderly can be attributed to several
pathophysiological mechanisms. Aging can lead to
chronic itch through loss of skin barrier function, immunosenescence and neuropathic changes (Fig. 1) [24].
In addition, multiple cutaneous, systemic and psychogenic
conditions have been related to chronic itch in the elderly
[24].

Fig. 1 Changes in elderly skin


that may lead to chronic itch

Chronic Pruritus in the Elderly

itch had decreased SC water content and increased intracorneal cohesion [21]. This suggests that itch and xerosis
may be related to an acquired abnormality of keratinization, as well as decreased water content within the SC [21].
The SC is composed of an ILM. The ILM participates in
cellular turnover and maintenance of normal barrier function [22]. The ILM is composed of ceramides, cholesterol
and free fatty acids [22]. This lipid mixture originates from
lamellar bodies in the stratum granulosum [23]. Geriatric
patients have been found to have decreased levels of ceramides within the SC. This may be secondary to decreased
levels of ceramide-generating enzymes [24]. Additionally,
diminished secretion of lamellar body contents into the
intercellular area has been reported in geriatric skin [25].
Aquaporin 3 (AQP3) is a water-transporting protein.
AQP3 facilitates transport of water and glycerol through
the cell membrane to maintain epidermal hydration. Lack
of AQP3 channels has been related to dry skin [26]. Decreased AQP3 expression has been shown in elderly skin
and may be involved in the aging process [27]. However,
the specific function of AQP3 in the pathophysiology of
itch has not yet been elucidated.
The pH of elderly skin becomes more alkaline with age
[2830]. pH changes in the skin can affect enzymatic activity within the SC [31]. As a result of the altered enzymatic activity, skin may become dry because of decreased
production of natural moisturizing factor [29], reduced
activity of ceramide-forming enzymes [32, 33] and decreased lamellar body secretion [34]. Furthermore, alkaline
pH increases the activity of serine proteases in the skin,
leading to activation of protease-activated receptor 2
(PAR2) receptors, which induce itch [34, 35]. Therefore,
changes in pH may induce or exacerbate chronic itch in the
elderly population.
SC proteases and their inhibitors are a large group of
enzymes, which contribute to the desquamation process
and maintenance of barrier function in normal skin [36].
Although reduction of some proteases has been related to
dry skin [36], the role of proteases in xerosis and itch is not
clear. Previous studies have shown opposing results [37].
More research is needed to better understand how SC
proteases are related to xerosis in the elderly.
Other factors that may lead to dry skin include decreased activity of sebaceous and sweat glands [38, 39],
and decreased levels of hormones, particularly oestrogens,
in women [40]. Further exploration is needed in order to
determine if these factors contribute to the development of
chronic itch.
3.2 Immunosenescence of the Skin
The transformation of the immune system during the process of aging, known as immunosenescence, has been

203

related to some forms of chronic pruritus. Immunosenescence affects both innate and adaptive immunity, and has
been associated with increased levels of autoreactivity [2,
4]. Studies have suggested that bullous pemphigoid (BP),
which is more common in the elderly, may manifest with
itch and a nonspecific urticarial rash accompanied by circulating autoantibodies. This presentation may precede the
full development of BP, which is characterized by an extremely itchy, blistering dermatosis [41].
3.3 Neuropathic Itch
Chronic itch in the elderly can also be neuropathic in origin. Neuropathic itch (NI) can result from central or peripheral nerve damage acquired during the aging process
[2, 4, 42]. Several conditions involving NI have been described in the geriatric population.
The most common sensory ganglionitis known to cause
NI is shingles (herpes zoster) [43]. Shingles is the most
common cutaneous viral infection in the elderly [9, 44].
The rate of persistent pruritus following resolution of the
shingles rash (postherpetic pruritus) is reported to be as
high as 36 % [45]. Activation of itch-inducing neurons in
the affected dermatome is a possible explanation for this
form of itch [46].
Diabetes mellitus is the most common cause of small-fibre
polyneuropathy in developed countries [43]. As a result,
diabetic patients can develop NI [47]. A recent study in Japan
mentioned truncal pruritus as a frequent clinical manifestation of neuropathy in diabetic patients [47]. Furthermore, a
study done by the authors found that the presence of diabetes
correlates with scalp itch in geriatric patients [1]. Therefore,
scalp itch may be of neuropathic origin [48].
Nerve compression is another cause of chronic pruritus
in the elderly [43]. Two forms of radiculopathy that have
been related to itch in the elderly are brachioradial pruritus
(BRP) and notalgia paraesthetica (NP).
BRP clinically manifests as pruritus localized to the
extensor forearms and distal arms, but it can also include
the proximal arms, shoulders, neck, back and chest [49].
This form of pruritus is often bilateral and limited to the
upper body. In rare cases, it may be generalized or unilateral, or it may affect the lower extremities [50]. In
elderly patients, brachioradial itch can also be secondary to
nerve compression by tumours [51].
Patients with NP often present with unilateral itch affecting the interscapular region [52]. The area affected is
usually located between the second and sixth posterior
thoracic roots. Patients may also complain of pain, tingling,
numbness or pricking [53]. Physical examination may reveal normal skin or a patch of reticular hyperpigmentation
secondary to chronic scratching. In rare cases, NP may also
be localized to other areas of the body [54].

204

Lichen simplex chronicus (LSC) is a common dermatological condition in the geriatric population [55]. LSC
presents clinically with lichenification, which develops as a
consequence of continuous scratching. Common areas of
involvement include the scalp, neck, genital area, arms,
ankles and shins [55]. The pathogenesis of itch in LSC is
not clear, although a neuropathic origin has been proposed
[56]. Thus, LSC may be considered a form of NI [57].
Furthermore, an association between LSC and depression
has been mentioned [58]. There is a high rate of depression
in the elderly population [59]. Consequently, it is important
to evaluate patients with LSC for depression.
3.4 Cutaneous Conditions
In addition to xerosis, multiple dermatological conditions
have been related to chronic itch in the elderly. Of note,
geriatric patients with dermatoses have been reported to
suffer from itch of higher intensity [1].
Seborrhoeic dermatitis (SD) is a chronic skin condition,
characterized by erythematous patches and plaques with
overlying adherent, greasy scales. SD predominantly affects oily areas of the body, such as the scalp, eyebrows,
eyelids, periauricular area, nasolabial folds, cheeks, sternal
area and interscapular areas. It may also affect other body
folds [55]. The reported prevalence of SD in the geriatric
population is 31 % [60]. Within the elderly population, SD
has been associated with localized itch [61, 62]. SD is a
particularly common skin manifestation in elderly patients
with Parkinsons disease, depression or anxiety [63, 64].
Contact dermatitis results from direct skin exposure to a
chemical substance [65]. Studies have determined that the
prevalence of allergic contact dermatitis in the elderly is
between 33 and 64 % in European countries [66]. Traditionally, contact dermatitis is divided into allergic and irritant forms. Allergic contact dermatitis consists of a
reaction to an external stimulus that is mediated by the
adaptive immune system, whereas irritant contact dermatitis consists of a nonspecific reaction that is mediated
by the innate immune system. Risk factors for the development of contact dermatitis in the elderly are skin barrier
defects and immunosenescence [67]. In addition, in the
context of decreased barrier function, topical medications
may cause contact dermatitis and should be prescribed with
caution in elderly patients [68].
Nummular eczema (NE) is an extremely pruritic skin
condition, characterized by coin-shaped plaques. NE is an
inflammatory skin disease found in elderly patients [61]
and can be considered a late-onset form of atopic dermatitis
[69]. A previous study showed decreased epidermal nerve
fibres in patients with NE compared with healthy controls
[70]. Furthermore, it has been suggested that the density of
epidermal nerve fibres decreases with age [71]. It is

R. Valdes-Rodriguez et al.

important to explore the role of other itch-inducing inflammatory mediators, such as mast cell enzymes and
proteases, in the physiopathology of NE itch.
Chronic venous insufficiency (CVI) is defined as a retrograde flow of blood in the lower extremities as a result of
valvular incompetence. There are several skin manifestations of CVI, such as telangiectasias, reticular veins, varicose veins, oedema, pigmentation and lipodermatosclerosis
[72]. The presence of CVI-related skin changes increases
the risk of chronic pruritus in elderly patients [1]. It is
important to be aware of this association when assessing
chronic itch in the lower extremities of geriatric patients.
Psoriasis is a chronic inflammatory disease, which is
commonly seen in the elderly population [73]. Associations
have been made between psoriasis and metabolic syndrome, cardiovascular diseases, malignancy and psoriatic
arthritis. Itch is the most common symptom in elderly
psoriatic patients [74]. A study done in South Korea in
patients with adult-onset psoriasis (aged 60 years and
older) found that 75 % of patients suffered from chronic
itch and 35 % suffered from moderate to severe itch that
interrupted normal daily activities [73]. It is also necessary
to evaluate the genital area in patients with psoriasis because of the high prevalence of genital itch in this
population [75].
Chronic idiopathic urticaria (CIU) is a pruritic condition, characterized by the presence of wheals on a neardaily basis for greater than 6 weeks. CIU is common in the
elderly [61]. In CIU, pruritus has been described as
stinging, tickling, or burning in nature. The itch is often
worse at night and may be triggered by ambient heat and
sweating. In addition, itch intensity in CIU has been associated with stress [76].
Transient acantholytic dermatosis, or Grovers disease
(GD), was first described in 1970 [77]. It is characterized
by very pruritic papules and papulovesicles affecting the
trunk and proximal limbs. This disease most commonly
affects elderly Caucasian men. Several factors have been
related to GD, such as exposure to sunlight, hot temperatures and sweat. GD has also been associated with
malignancies and reaction to cutaneous infection [77, 78].
However, the exact pathophysiology of this condition remains unclear. Tumour necrosis factor (TNF)-a and other
inflammatory mediators are possible causes of itch in this
disease [79].
Scabies is a parasitic infestation caused by the mite
Sarcoptes scabiei (var. hominis) [80]. Scabies is an extremely itchy condition found with increased prevalence in
patients residing in nursing homes and geriatric wards [81].
Scabies presents clinically with severe, generalized itch
that may be especially strong at night. However, it is important to note that nocturnal itch is not specific to this
condition. In elderly patients, misdiagnosis can lead to

Chronic Pruritus in the Elderly

unnecessary use of topical steroids, with a delay in proper


diagnosis and treatment [82]. Patients who use topical or
systemic immunosuppressant drugs, who have altered cutaneous sensation or who suffer from immunosuppression
secondary to systemic conditions are at risk of developing
crusted scabies (Norwegian scabies) [83]. The presence of
itch in scabies has been associated with a cellular immune
response; however, the exact mechanism of itch pathogenesis is unknown.
Basal cell carcinoma (BCC) is the most common type of
malignancy in humans and the most common skin cancer
in the elderly [84]. Although itch has not often been
mentioned as a common symptom, a recent large study
found that 32 % of patients with BCC had itch. The degree
of inflammation and the type of inflammatory infiltrate
have been correlated with itch intensity in BCC [85].
Cutaneous T cell lymphoma (CTCL) is a non-Hodgkins
lymphoma, which encompasses multiple subgroups.
Clinically, advanced stages of CTCL, such as tumoral
mycosis fungoides or erythroderma, present with intense
itch. When CTCL is suspected, skin biopsy is required in
order to define the subtype and determine the most appropriate treatment. Increased interleukin (IL)-31 expression has been associated with itch in patients with CTCL
[86].
3.5 Systemic Conditions
Numerous systemic conditions, including neoplasms, neural conditions, infectious conditions [e.g. human immunodeficiency virus (HIV)] and liver disease, have been
related to chronic itch in the elderly. Systemic conditions
may cause itch with or without the presence of a rash.
Itch associated with chronic kidney disease (CKD) may
be referred to as uremic pruritus or CKD itch. The presence
of CKD itch in the general population varies, with prevalence rates of 1549 % in patients with chronic kidney
insufficiency and 5090 % in patients on haemodialysis.
Improvement in dialysis techniques has decreased the
prevalence to 42 %. However, itch continues to have a
highly deleterious impact on quality of life in dialysis patients [87]. The prevalence of CKD itch in geriatric patients
has not been assessed. The glomerular filtration rate decreases with age. It is of interest to determine if there is any
correlation between chronic itch and a decrease in the
glomerular filtration rate.
The elderly population is at increased risk of developing
malignancies [88]. Itch related to cancer is known as
paraneoplastic itch and was recently defined as the sensation of itch as a systemic reaction to the presence of a
tumor or a hematological malignancy neither induced by
the local presence of cancer cells nor by tumor therapy. It
usually disappears with remission of the tumor and can

205

return with its relapse [89]. Multiple case reports and


some clinical studies have reported generalized itch as an
important skin symptom in cancer patients [78, 90].
However, in elderly patients, studies examining the
prevalence and characteristics of paraneoplastic itch are
lacking. In a 6-year follow-up study, which included 125
patients with generalized pruritus, eight patients aged
5982 years had itch attributable to malignancy (lymphoma, stomach, breast, lung or renal cancer) [91]. A large
cohort study found that the presence of chronic itch without
dermatological manifestation is a risk factor for having
undiagnosed haematological and bile duct malignancies
[92]. It is important to have a high index of suspicion for
malignancy in elderly patients during the first year of newonset itch without a rash. Low-grade lymphoma and other
haematological malignancies, including chronic lymphocytic leukaemia (CLL) and multiple myeloma, are common
in old age and are associated with chronic itch [93].
Chronic itch that is attributable to hepatobiliary disease
is known as cholestatic pruritus. The prevalence of
cholestatic pruritus varies according to the aetiology of the
hepatobiliary disease [94]. Cholestatic pruritus can cause
significant morbidity in patients with liver disease [94].
Recent evidence has implicated autotaxin (ATX) and
lysophosphatidic acid (LPA) as potential mediators of
cholestatic pruritus [95]. In severe cases, liver transplantation may be the only treatment capable of fully reliving
itch in the context of chronic liver disease [96].
Stroke occurs with a high incidence in the elderly
population [97]. Itch has been anecdotally reported as a
post-stroke complication. Patients often present days or
weeks after a stroke with complaints of new-onset itch
[98]. These patients usually have normal skin findings or
scratching-induced changes on physical examination. Itch
associated with cerebrovascular accidents often presents on
the side contralateral to that of the brain damage [43, 98].
Infarction of the lateral medulla can lead to a specific
presentation of itch known as trigeminal trophic syndrome
(TTS). This condition is characterized by intense pruritus
in addition to facial ulceration in the area of distribution of
the trigeminal nerve [99].
In HIV patients, chronic itch is reported to be one of the
most common dermatological complaints that affect quality of life [100]. Although there are currently no reports on
HIV and chronic itch in the elderly, it is important to
consider that life expectancy in HIV patients has been increasing over the past few years [101]. In 2006, 2 % of new
cases of HIV reported by the Centers for Disease Control
and Prevention (CDC) were subjects aged 65 years or older
[102]. It is therefore important to better understand the
pathogenesis and treatment of chronic itch in elderly HIV
patients. Furthermore, since many patients with HIV are
treated with a variety of medications, it is of interest to find

206

targeted antipruritic agents in order to avoid unnecessary


drug interactions and side effects.
Hyperthyroidism has been associated with generalized
chronic pruritus. A casecontrol study determined itch to
be a common symptom in hyperthyroid patients [103].
More research is needed to examine a possible correlation
between thyroxine and itch.
Pruritus may also develop as an adverse reaction to use
of medications [104]. In the geriatric population,
polypharmacy is a risk factor for the development of drugrelated itch [4]. Multiple medications have been reported to
cause itch [104]. Calcium channel blockers have been associated with chronic pruritus in elderly patients [105].
Other medications that have been mentioned as possible
causes of itch in this population are angiotensin-converting
enzyme inhibitors, thiazides [106], salicylates, chloroquine
and codeine [4, 61]. Itch related to medication use may
present with or without a rash and may be acute (lasting
less than 6 weeks) or chronic. It may present hours, weeks,
months or years after drug ingestion. It may appear following the first dose of medication or at any other time
during a treatment regimen [107]. The pathophysiology of
drug-induced pruritus has not yet been elucidated and may
be multifactorial [104]. When a medication is suspected to
be the cause of itch, it should be discontinued. However,
itch may persist for months following cessation of
medication use.
3.6 Psychogenic Conditions
Psychogenic pruritus (PP) commonly presents in subjects
with underlying psychiatric conditions and is characterized
by an intense impulse to scratch, gouge, pick or squeeze at
normal skin [108, 109]. Multiple psychiatric disorders have
been related to itch: depression, obsessive compulsive
disorder, anxiety, somatoform disorders, mania, psychosis,
substance abuse and delusion of parasitosis [110]. Mental
disorders have a high prevalence in the geriatric population
[111]. Depression and anxiety disorders are especially
common in elderly patients [112, 113].
Chronic itch in certain dermatological conditions, such
as psoriasis, LSC, NE and itch localized to the scalp and
genital area, is common in the elderly and can be exacerbated by anxiety or stress [114116]. Better understanding
of this relationship may lead to more optimal treatments.

R. Valdes-Rodriguez et al.

longer than 6 weeks. Several characteristics of itch should


be assessed, including the intensity and temporal pattern, as
well as ameliorating and exacerbating factors. In addition,
a thorough review of systems should be performed to
assess for constitutional symptoms that may indicate the
presence of a systemic condition [117].
It is important to determine the past medical history as
well as the social history. Alcohol or drug abuse should be
noted, as this can be associated with systemic itch-causing
conditions, such as liver insufficiency. Old and new
medications should be listed [117].
It is necessary to determine if family members suffer
from chronic itch as well. Also, if the patient comes from a
nursing home, it is important to determine if other residents
suffer from itch, as this may suggest scabies as an underlying cause.
A full-body physical examination should be performed.
In order to determine whether itch is related to a dermatological condition, the entirety of the patients skin should
be evaluated (Fig. 2). A rash may or may not be present.
When a patient presents with a nonspecific rash, a skin
biopsy should be performed. It is also important to examine
the adnexal structures, including the hair and nails, for
signs of underlying dermatological and systemic conditions, which may help determine the aetiology of pruritus
[61].
In the context of the history and physical examination,
laboratory tests may be ordered. Recommended panels
include a complete blood cell count, basic metabolic profile, liver function tests, thyroid function tests and the
erythrocyte sedimentation rate. Imaging studies should be
considered on a case-dependent basis. In patients with itch
confined to a specific dermatome, is important to consider
evaluation with magnetic resonance imaging [118].
For elderly patients with new-onset chronic itch that has
developed within the past 6 months, it is important to include the possibility of cancer in the differential diagnosis.
The initial workup for diagnosis should include a thorough
history and physical examination, including lymph node
assessment. Laboratory tests, including a complete blood
cell count and liver function tests, should be considered, as
well as imaging studies in some cases [89]. The diagnostic
workup should be directed by the clinical evaluation and
the index of suspicion. Cancers that have been associated
with chronic itch include myeloproliferative disorders,
liver cancer and prostate cancer [119].

4 Workup of the Patient With Chronic Itch


5 Management
When a patient presents with pruritus, history taking is the
most important factor for reaching an accurate diagnosis.
First, it is important to determine whether the patient has
acute or chronic itch. Chronic itch is defined as itch lasting

The treatment of chronic pruritus is uniquely challenging in


the elderly population. The presence of physical and cognitive limitations, comorbidities and polypharmacy

Chronic Pruritus in the Elderly

207

Elderly paent with chronic itch

No primary skin lesions


Non-dermatologic cause

Dermatologic cause

Recognizable dermatologic
cause
Xerosis
Seborrheic dermas
Contact dermas
Lichen simplex chronicus
Psoriasis
Nummular eczema
Scabies

No recognizable
dermatologic cause
Neuropathic itch

Skin biopsy
(Bullous
pemphigoid)

Nerve
Impingement
Brachioradial
pruritus
Notalgia
parestheca
Aected
dermatome

MRI

Post herpec
Diabetes
mellitus smallber polyneuropathy
Scalp itch

Systemic causes

Psychogenic itch

Chronic kidney
disease
Cholestac liver
disease
Hematological
Malignancy
HIV infecon

Anxiety
Depression

Complete blood count


Erythrocyte sedimentaon
rate
Creanine level
Liver funcon test
Thyroid funcon test
HIV serology analysis
Chest radiography

Fig. 2 Proposed workup for elderly patients with chronic itch. HIV human immunodeficiency virus, MRI magnetic resonance imaging

necessitate management that is specifically tailored to each


individual. Also, use of unnecessary or redundant
medications should be avoided, as this may lead to significant morbidity in the elderly population [120].
Patient education is an important component of successful treatment of pruritus [121]. Patients should be informed that scratching creates cutaneous inflammation and
should be avoided whenever possible. Fingernails should
be kept short to minimize damage caused by scratching. In
addition, patients should be informed that using cool or
lukewarm water during bathing may reduce itch. Moisturizers should be applied immediately after bathing in
order to maximize their efficacy. Cleansers with a high pH
or those that contain alcohol should be avoided [122]. It is
important to provide education to those responsible for the
care of elderly patients as well.
In conditions such as scabies, CKD itch, cholestatic
pruritus, paraneoplastic pruritus and others, itch may resolve with treatment of the underlying condition. Therefore, therapeutic efforts should be directed accordingly.
However, in some cases, symptomatic treatment may be
required. The following topical treatments (see Table 1)

and systemic treatments (see Table 2) have been found to


be efficacious in controlling chronic pruritus in dermatological, neuropathic and systemic conditions.
5.1 Topical Treatments
Emollients should serve as first-line therapy for localized
itch, itch associated with CKD, and xerosis [122, 123].
They optimize skin barrier function and prevent excess
transepidermal water loss. Acidic topical treatments
(pH 4.56) help maintain a low pH within the skin surface
and reduce the activity of itch-inducing serine proteases
[124, 125].
Baths containing oatmeal are a simple treatment option
and may complement other therapies in patients with
chronic itch. Oatmeal contains antioxidants and anti-inflammatory mediators, which have been shown to reduce
cutaneous inflammation [126]. These baths may be taken
up to once per day and should be 1520 min long.
Topical salicylic acid, a cyclooxygenase inhibitor, has
been shown in a double-blind, crossover placebo trial to
significantly reduce pruritus in patients with LSC [127].

208

R. Valdes-Rodriguez et al.

Table 1 Topical treatments


Medications

Mechanisms of action

Therapeutic indications

Emollients

Improve skin barrier


function

Xerosis, NE, psoriasis, LSC, contact dermatitis, CKD itch

Salicylic acid

Keratolytic agent

LSC, psoriasis

Urea

Keratolytic agent

Xerosis, CKD itch, NE, atopic dermatitis, contact dermatitis, psoriasis

Menthol

TRPM8 agonist

Chronic itch

Capsaicin

TRPV1 agonist

NI, CKD itch

Corticosteroids

Anti-inflammatory agents

Inflammatory skin diseases, e.g. NE, psoriasis, contact dermatitis, LSC,


atopic dermatitis

Pimecrolimus, tacrolimus

Calcineurin inhibitors

NE, psoriasis, contact dermatitis, SD, atopic dermatitis

Pramoxine (pramocaine)

Local anaesthetic

NI, scalp itch, CKD itch

Doxepin

H1 and H2 antagonist, TCA

Atopic dermatitis

Strontium

Calcimimetic ion channel


inhibitor

NI, NE

Topical ketamine with amitriptyline and


lidocaine

Ion channel blockers

NI

CKD chronic kidney disease, H1 and H2 histamine receptors 1 and 2, LSC lichen simplex chronicus, NE nummular eczema, NI neuropathic
itch, SD seborrhoeic dermatitis, TCA tricyclic antidepressant, TRPM8 transient receptor potential melastatin 8, TRPV1 transient receptor potential vanilloid 1

Salicylic acid is a keratolytic agent, which serves to


counteract scratching-induced thickening of the skin. The
antipruritic effect of salicylic acid may be related to local
desensitization of itch fibres.
The level of urea, a natural moisturizing factor, has been
shown to be decreased within the SC of elderly patients
[128]. While studies on the efficacy of urea solutions in
chronic pruritus are limited, the use of urea may be
beneficial in a variety of pruritic conditions, including
xerosis, CKD itch, NE, atopic dermatitis, contact dermatitis
and psoriasis [129].
Menthol is often used as a topical antipruritic agent at
concentrations of 15 %. It activates the transient receptor
potential melastatin 8 (TRPM8) receptor on A-delta afferents to elicit a cooling sensation [130]. However, the
effect of menthol lasts less than 30 min, and its use may be
limited by its short-term efficacy. Higher concentrations
may cause hypersensitivity and transient burning
sensations.
Capsaicin has been used in the treatment of postherpetic
neuralgia, NP and BRP. Its causes local desensitization of
peripheral nerves, perhaps through activation of transient
receptor potential vanilloid 1 (TRPV1) receptors [131].
Additionally, capsaicin has been shown to be effective in
the treatment of uraemic pruritus in patients undergoing
haemodialysis [132]. However, capsaicin may cause a
burning sensation during the first 2 weeks of usage, and
this may limit compliance, especially in elderly patients.
Pre-treatment with EMLA (lidocaine/prilocaine), a topical anaesthetic, has been shown to significantly reduce this
burning sensation [133].

Topical corticosteroids in chronic itch may be used in


dermatological conditions such as psoriasis, LSC or NE, in
which inflammation is the underlying aetiology. These
agents are known to cause thinning of the skin, which may
be especially problematic in the elderly population.
Therefore, long-term use should be avoided whenever
possible. If long-term use is required, close follow-up is
imperative [134].
Pimecrolimus and tacrolimus have been shown to be effective treatments for pruritus in patients with atopic dermatitis. In addition, they may also be beneficial treatments
for pruritus associated with contact dermatitis and SD [135].
Side effects include burning and stinging sensations.
Pramoxine, a local anaesthetic, has been shown to reduce itch in patients with CKD [136]. Side effects include
skin irritation and dryness at the site of application.
Topical strontium in a 4 % formulation was recently
shown in one double-blind, vehicle-controlled trial to be
effective in reducing both the duration and the peak intensity of experimentally induced itch in humans [137].
Strontium can be used therapeutically for itch secondary to
xerosis, NE or LSC.
Topical 5 % doxepin cream, a potent H1 and H2 antagonist, has been shown in a randomized, controlled trial
to reduce pruritus in patients with atopic eczema. Side
effects may include localized stinging or burning sensations, and drowsiness [138].
A topical amitriptylineketamine combination has been
shown to be an effective treatment for localized pruritus of
various neuropathic origins. This treatment acts through
local inhibition of sensitized A- and C-fibres. This topical

Chronic Pruritus in the Elderly

209

Table 2 Systemic treatments


Medications

Mechanisms of actions

Therapeutic indications

Side effects

H1 receptor antagonist

Nocturnal itch, paraneoplastic itch

Drowsiness, dry mouth

H1 receptor antagonist

Chronic urticaria

Headache, dry mouth, urinary retention

Mirtazapine

SNRI

CTCL, CKD itch, cholestatic itch,


nocturnal itch

Dry mouth, increase in appetite, weight gain,


drowsiness

Paroxetine

SSRI

Solid carcinomas, atopic dermatitis

Dry mouth, sexual dysfunction, insomnia

Amitriptyline

TCA

NI

Urinary retention, constipation, dizziness,


dry mouth, cardiac abnormalities, blurred vision

Doxepin

TCA, H1 receptor
antagonist

Chronic urticaria, psychogenic itch, NI

Drowsiness, dry mouth, QT-interval prolongation

Antihistamines
First-generation
Hydroxyzine
Diphenhydramine
Second-generation
Cetirizine
Loratadine
Fexofenadine
Antidepressants

Fluvoxamine
Sertraline

CKD itch, cholestatic itch

Opioid receptor agonists and antagonists


Naltrexone

Mu-opioid antagonist

Cholestasis, atopic dermatitis

Nausea, loss of appetite, diarrhoea,


hepatotoxicity, reversal of analgesia

Butorphanol

Mu-opioid antagonist,
kappa-opioid agonist

Intractable pruritus

Somnolence, dizziness, nausea

Nalfurafine

Kappa-opioid agonist

CKD itch in haemodialysis

Headache, insomnia

GABA agonist

CKD itch, NI, paraneoplastic itch

Drowsiness, weight gain, constipation,


leg swelling, blurred vision

Antiepileptics
Gabapentin
Pregabalin

Drowsiness, weight gain, leg swelling

Immunomodulatory agent
Thalidomide

Neuropathic TNF
inhibitor

CKD itch, NI, paraneoplastic itch

Somnolence, peripheral neuropathy, DVT

NK1 receptor antagonist

CTCL

Weakness, dizziness

Immunomodulatory agent

Psoriasis, atopic dermatitis, CTCL,


cholestatic itch, HIV-associated itch

Increased risk of skin cancer

Substance P antagonist
Aprepitant
Phototherapy
UV phototherapy

CKD chronic kidney disease, CTCL cutaneous T cell lymphoma, DVT deep vein thrombosis, GABA gamma-aminobutyric acid, H1 histamine
receptor 1, HIV human immunodeficiency virus, NI neuropathic itch, NK1 neurokinin-1 receptor, SNRI selective norepinephrine reuptake inhibitor, SSRI selective serotonin reuptake inhibitor, TCA tricyclic antidepressant, TNF tumour necrosis factor, UV ultraviolet

combination may be useful for patients with BRP, NP or


postherpetic itch [139]. The addition of lidocaine to this
formulation has been used in clinical practice with
beneficial results.
5.2 Systemic Treatments
Antihistamines: First-generation antihistamines (hydroxyzine, diphenhydramine) and second-generation antihistamines (cetirizine, fexofenadine, loratadine) have been
shown in randomized, controlled trials to have antipruritic

effects [140]. Second-generation antihistamines are useful


in the treatment of histamine-mediated pruritic conditions,
such as chronic urticaria [141]. First-generation antihistamines may also be useful in helping patients who experience nocturnal pruritus to sleep at night, because of their
soporific effects. Side effects of these medications include
drowsiness, confusion, dry mouth and urinary retention. Of
note, hydroxyzine is particularly lipophilic and will have a
prolonged half-life in elderly patients [120].
Selective Norepinephrine Reuptake Inhibitors: The selective norepinephrine reuptake inhibitor (SNRI)

210

mirtazapine has been shown in case reports to be an effective treatment for pruritus in patients with chronic leukaemia, systemic lymphoma, CTCL, CKD or cholestasis
[142, 143]. Mirtazapine has also been shown in a case
series to be effective in treating nocturnal itch [144]. Additionally, mirtazapine may be useful in treating chronic
pruritus in patients with comorbid anxiety and/or depression. Side effects include drowsiness, dry mouth, increase
in appetite and weight gain.
Selective Serotonin Reuptake Inhibitors: The selective
serotonin reuptake inhibitors (SSRIs) paroxetine and fluvoxamine have been reported in a single prospective study
to have an antipruritic effect in patients with atopic dermatitis, systemic lymphoma or solid carcinomas [145].
Additionally, sertraline has been shown in a randomized,
double-blind, placebo-controlled trial to reduce pruritus
associated with chronic liver disease [146]. Side effects of
paroxetine may include insomnia, dry mouth and sexual
dysfunction.
Tricyclic Antidepressants: Amitriptyline has been reported in case series to be useful treating NI [108]. However, the elderly are particularly susceptible to the
anticholinergic side effects of this agent, such as urinary
retention, constipation, dizziness, dry mouth, cardiac conduction abnormalities and blurred vision. Doxepin, which
acts as both a tricyclic antidepressant (TCA) and an
H1 antagonist, may be used to treat psychogenic itch and
NI [108].
Activation of mu-opioid receptors is known to stimulate
itch perception, whereas activation of kappa-opioid receptors is known to inhibit itch perception. Thus, treatments targeting opioid receptors may reduce the sensation
of itch but not the underlying cause [147].
Mu-Opioid Receptor Antagonists: Naltrexone has been
shown in randomized controlled trials to reduce itch associated with cholestasis and atopic dermatitis [147].
However, its side effects include nausea, loss of appetite,
diarrhoea, hepatotoxicity and reversal of analgesia. Consequently, these agents should be used with caution in the
elderly population.
Kappa-Opioid Agonists and Mu-Opioid Antagonists:
Butorphanol, administered intranasally, has been shown in
a small case series to be an efficacious treatment for
chronic, severe and intractable pruritus [148]. Its side effect
profile is preferable to that of pure mu-opioid antagonists
and includes somnolence, dizziness, nausea and vomiting.
Interestingly, a recent study showed that use of butorphanol
activates the same pleasure areas of the brain that have
been associated with relief from self-scratching [149].
Butorphanol may be administered just once daily, which
adds to its ease of use.
Kappa-Opioid Agonists: Nalfurafine has been shown in
randomized, placebo-controlled trials to reduce itch in

R. Valdes-Rodriguez et al.

patients with uraemic pruritus who are undergoing haemodialysis. However, it is not currently available in the
USA (available only in Japan). Side effects include headache and insomnia [150].
Analogues of Gamma-Aminobutyric Acid: Gabapentin
and pregabalin are effective antipruritic agents, which act
by inhibiting neuronal transmission. They are effective
treatments for itch due to CKD [151, 152] and may also be
useful in treating NI from conditions such as prurigo
nodularis, postherpetic itch and BRP [108, 153]. In the
elderly, doses should be started low (100300 mg at night
is suggested) and tapered up as necessary [120]. Side effects include drowsiness, weight gain, ataxia, leg swelling,
blurred vision and constipation. In addition, pregabalin
may induce withdrawal symptoms if stopped abruptly;
therefore, cessation should be tapered [154].
Thalidomide, an immunomodulatory agent, has been
used in the treatment of refractory pruritus due to CKD.
This agent was found to be efficacious in a crossover,
double-blind, randomized, controlled trial [155]. It has also
been mentioned as a potential treatment for paraneoplastic
itch [89].
Selective Neurokinin-1 Receptor Antagonists: Aprepitant
has been used in the treatment of chronic pruritus. Of note,
increased neurokinin-1 (NK1) expression on keratinocytes
of patients with chronic pruritus has been described. A case
report determined that aprepitant was useful in the treatment
of chronic pruritus secondary to Sezary syndrome and described no major side effects with its use [156].
Ultraviolet A (UVA), broadband ultraviolet B (BBUVB) and narrow-band UVB (NB-UVB)-based light
therapies are useful in the treatment of atopic dermatitis,
psoriasis and CTCL.
UVB phototherapy is effective in treating uraemic pruritus and may also be useful for cholestatic pruritus and
HIV-associated pruritus. In uremic pruritus, UVB phototherapy may provide itch relief through induction of
apoptosis of cutaneous mast cells [157]. Additionally, UVB
light has been shown to inhibit T-helper 1 (Th1)-mediated
immune responses and promote decreased IL-2 production
[158]. Advantages of phototherapy in the elderly include
avoidance of drug interactions and compliance issues.
However, disadvantages include an increased risk of skin
cancer, especially in Caucasians.
5.3 Psychological Treatments
Behavioural modification strategies may complement
pharmacotherapy in the treatment of chronic pruritus.
While few studies have been done on psychological treatments for chronic itch, cognitive behavioural therapy and
patient education may help reduce the frequency of itch
[121].

Chronic Pruritus in the Elderly

5.4 Holistic Approaches


In some cases, holistic therapies may be beneficial in the
treatment of chronic pruritus. Acupuncture has been studied as a treatment modality for chronic itch associated with
CKD and has been reported to have favourable effects.
However, strong evidence for the efficacy of this approach
is lacking [159]. A dietary approach to the treatment of
chronic pruritus is not recommended.
5.5 Treatment Recommendations: Xerosis-Associated
Chronic Itch
Xerosis is considered to be the most prevalent cause of
chronic pruritus in the elderly population. The management of this common condition must be focused on both
healing current damage within the SC and preventing
future breakdown of barrier function. It is recommended
that patients suffering from xerosis bathe in tepid water,
avoid using soaps (because of their high pH) and use a
non-irritating cleanser. Brands that are known to have an
acidic pH and have been personally recommended include Cetaphil, Sebamed, and Vanicream. In addition, patients should be advised to gently pat their skin
dry after bathing, instead of rubbing it vigorously.
Moisturizers should be applied liberally after bathing in
order to maximize the barrier function of the SC. Also,
since fluctuations in temperature and humidity may
trigger pruritus, use of humidifiers in the winter months
and air conditioners in the summer months may be
helpful. Systemic treatments can be considered for severe
cases.

6 Conclusion
As the elderly population grows in size, it is important
to better understand the pathophysiology and treatment
of chronic itch, a prevalent symptom in this subset of
patients. Determination of the aetiology of pruritus must
be made, whether due to neuropathic, immunosenescent
or cutaneous origin. In some cases, numerous comorbidities may make this a challenge. Treatment must be
selected carefully, accounting for the presence of
polypharmacy, cognitive limitations and potential for
adverse effects. Management should be tailored to each
individual in order to achieve maximum compliance and
efficacy.
Acknowledgments The authors thank Eilen Flores Ortiz for assistance in preparing Fig. 1.
Funding No sources of funding were used to support the preparation of this article.

211
Conflicts of interest Rodrigo Valdes-Rodriguez and Carolyn Stull
declare no conflicts of interest. Gil Yosipovitch is a member of scientific advisory boards for Cosmoderm, TREVI, Velocity and Creabilis and is funded by GSK-Stiefel and the LEO Foundation.

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