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Rodrigo Valdes Rodriguez
Temple University
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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
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
202
R. Valdes-Rodriguez et al.
2 Epidemiology
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].
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
205
206
R. Valdes-Rodriguez et al.
207
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
Fig. 2 Proposed workup for elderly patients with chronic itch. HIV human immunodeficiency virus, MRI magnetic resonance imaging
208
R. Valdes-Rodriguez et al.
Mechanisms of action
Therapeutic indications
Emollients
Salicylic acid
Keratolytic agent
LSC, psoriasis
Urea
Keratolytic agent
Menthol
TRPM8 agonist
Chronic itch
Capsaicin
TRPV1 agonist
Corticosteroids
Anti-inflammatory agents
Pimecrolimus, tacrolimus
Calcineurin inhibitors
Pramoxine (pramocaine)
Local anaesthetic
Doxepin
Atopic dermatitis
Strontium
NI, NE
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
209
Mechanisms of actions
Therapeutic indications
Side effects
H1 receptor antagonist
H1 receptor antagonist
Chronic urticaria
Mirtazapine
SNRI
Paroxetine
SSRI
Amitriptyline
TCA
NI
Doxepin
TCA, H1 receptor
antagonist
Antihistamines
First-generation
Hydroxyzine
Diphenhydramine
Second-generation
Cetirizine
Loratadine
Fexofenadine
Antidepressants
Fluvoxamine
Sertraline
Mu-opioid antagonist
Butorphanol
Mu-opioid antagonist,
kappa-opioid agonist
Intractable pruritus
Nalfurafine
Kappa-opioid agonist
Headache, insomnia
GABA agonist
Antiepileptics
Gabapentin
Pregabalin
Immunomodulatory agent
Thalidomide
Neuropathic TNF
inhibitor
CTCL
Weakness, dizziness
Immunomodulatory agent
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
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].
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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