Tejesh Patel, MD1 and Gil Yosipovitch, MD2,3
1. Division of Dermatology, Department of Medicine, University of Tennessee Health Science Center, Memphis, TN, USA
2. Department of Dermatology, Wake Forest University School of Medicine, Winston-Salem, NC, USA
3. Department of Neurobiology and Anatomy, Wake Forest University School of Medicine, Winston-Salem, NC, USA
The elderly in North America represent the fastest growing segment of the population and the most common skin complaint in this age group is pruritus. The multitude of variables that come with advanced age means that the management of pruritus in the elderly poses a particular therapeutic challenge. Pruritus in advanced age may result from a variety of etiologies, although xerosis is the most common. In addition, certain cutaneous and systemic diseases that are associated with pruritus are more prevalent in the elderly. At present, there is no universally accepted therapy for pruritus. Currently, management of pruritus in the elderly must take an individualistically tailored approach with consideration of the patient’s general health, the severity of symptoms, and the adverse effects of treatment. Physical and cognitive limitations, multiple comorbid conditions, and polypharmacy are some aspects that can influence the choice of treatment in this age group.
aging skin, comorbidity, itch, pruritus, xerosis
Pruritus is the most common skin complaint in patients over the age of 65 years.1,2 This often neglected symptom can have a profound impact on the quality of life in the elderly, especially through sleep deprivation. Given the multitude of variables that come with advanced age, the management of pruritus in the elderly poses a particular clinical challenge.
Pruritus in advanced age may result from a variety of etiologies. Xerosis (dry skin), which increases with age, is probably the most common cause of pruritus in the elderly.3,4 As skin ages, the integumentary and vascular systems undergo atrophy, leading to suboptimal moisture retention. However, many elderly patients have pruritic skin without xerosis. Other skin changes in advanced aged patients that may contribute to itch include decreased skin surface lipids and clearance of transepidermally absorbed materials from the dermis, reduced sweat and sebum production, as well as diminished barrier repair.4
A decline of normal immune function that occurs with aging also produces a higher incidence of autoimmune skin disorders that can induce pruritus, such as bullous pemphigoid and postherpetic neuralgia. Additional factors may also play a role, such as age-related changes in nerve fibers and polypharmacy. Certain cutaneous and systemic disorders that are associated with pruritus are also more prevalent in advanced aged patients (as discussed below). However, in many instances, no apparent cause is found.
A detailed history, review of systems, and physical examination are of prime importance in guiding antipruritic treatment of senescent skin. Once cutaneous and systemic causes of itch are excluded, idiopathic itch of the elderly may be considered. However, if an underlying cause is discovered, it should be addressed, as this frequently leads to symptomatic improvement. Certain pruritic cutaneous diseases are more prevalent in the elderly population, such as xerosis, nummular dermatitis, and seborrheic dermatitis. The later is especially common in patients with dementia and Parkinson’s disease. Systemic diseases that are associated with pruritus, such as chronic kidney disease, hepatic dysfunction, and endocrine disorders, are also more prevalent in the elderly. Notably, infectious etiologies of pruritus, including scabies and lice, may be more common in this age group especially within institutionalized care settings. In addition, medications frequently used in the elderly increase the possibility of drug-induced pruritus (e.g., aspirin, opioids, and angiotensin converting enzyme inhibitors). Another serious consideration in this cohort is that chronic pruritus may be a presenting sign of underlying malignancy (e.g., low grade lymphoma, multiple myeloma, and myleodysplastic syndromes), and thus, any case with a high index of suspicion necessitates a thorough work-up.5 Psychogenic and neuropathic disorders are also common causes in this age group.6
The management of pruritus in the elderly poses a particular challenge. Physical and cognitive impairments may make application of topical treatments impossible and compliance an issue. Comorbid conditions, especially those involving the liver and kidney, as well as the frequent polypharmacy in this age group, confers a greater risk of adverse drug reactions. At present, there is no universally accepted therapy for itch. Instead, management of pruritus, especially in the elderly, requires an individualistically tailored approach with consideration of the patient’s general health, the severity of symptoms, and the adverse effects of available treatments. Some of the treatments discussed are unlicensed for use in pruritus and should be administered under a specialist setting.
There are a number of general measures that may be useful in the management of pruritus in the elderly, irrespective of the underlying cause (Table 1). Patient education is central to the management of pruritus.7 Identifying and removing aggravating factors are often the initial steps in effective treatment. Breaking the “itch-scratch” cycle is critical and patients should be informed of the increased cutaneous inflammation that scratching causes. Simple measures, such as keeping finger nails short, may help to interrupt this vicious cycle. The sensation of pruritus is often heightened by warmth, thus, where appropriate, measures such as tepid showering, wearing light clothing, and the use of air conditioning should be undertaken to keep the skin cool. Wherever possible, simple topical regimens are preferable in order to maximize compliance and limit potential adverse drug reactions.
|General Measures to Reduce Pruritus|
|Table 1. General measures for the management of pruritus|
Moisturizers, Emollients and Barrier Creams
Moisturizers, emollients, and barrier repair creams are the mainstay of pruritus treatment in the elderly, especially in cases associated with xerosis. These nonpharmacologic compounds reduce pruritus through improving barrier function by helping to prevent transepidermal water loss and possibly preventing the entry of irritants and other itch-causing agents. Topical therapies with a low pH may be especially useful in optimizing the skin barrier function through their maintenance of the normal acidic pH of the skin surface. In addition, low pH topical therapies may be of further benefit through their reduction in the activity of serine proteases, such as mast cell tryptase, which is known to activate protease-activating receptor 2 (PAR2) on skin nerve fibers. This notion stems from recent studies suggesting serine proteases, via PAR2 located on C fiber terminals, may play an important role in mediating pruritus.8,9
Topical corticosteroids do not directly exert antipruritic effects, instead their therapeutic benefits are derived from their anti-inflammatory properties. Therefore, they should only be used to provide relief of itching that is associated with inflammatory skin diseases, such as nummular dermatitis or psoriasis. Topical corticosteroids should not be used to treat generalized chronic itch or for prolonged periods. Of note, the elderly are particularly vulnerable to the adverse effects (especially skin thinning) from the excessive use of topical corticosteroids.10
The topical calcineurin inhibitors, tacrolimus and pimecrolimus, have been shown to be effective in reducing pruritus in conditions such as chronic irritant hand dermatitis, seborrheic dermatitis, graft-versus-host disease, lichen sclerosis, anogenital pruritus, and prurigo nodularis.11 The antipruritic effects of topical calcineurin inhibitors may be mediated via TRPV1, a member of the transient receptor potential (TRP) family of excitatory ion channels, located on nerve fibers. Although the recognized side-effects of these agents include transient burning and stinging sensations, they are particularly useful in the elderly as there is no associated risk of skin atrophy.
Menthol, a naturally occurring cyclic terpene alcohol of plant origin, is frequently used as a topical antipruritic at concentrations of 1-3%. It has been shown that menthol elicits the same cooling sensation as low temperature through the TRPM8 receptor.12 Both cooling the skin and menthol use result in the relief of experimentally induced itch, although the latter is not associated with a decrease in skin temperature. Of note, elderly patients who report a reduction in pruritus with cooling may especially benefit from topical therapies containing menthol.12
Capsaicin has been reported to have a beneficial effect in chronic, localized pruritic disorders, particularly those of neuropathic origin, which are common in the elderly (e.g., postherpetic neuralgia, notalgia paresthetica, and brachioradial pruritus).13,14 The TRPV1 receptor has recently been implicated in the pathogenesis of pruritus and may be the target through which capsaicin exerts its antipruritic effect.15 A recognized side-effect is an initial intense transient burning sensation at the application site, which may lead to poor compliance, particularly in the elderly.
Pramoxine, a local anesthetic, reduces itch by interfering with transmission of impulses along sensory nerve fibers and has been shown to reduce pruritus in adult hemodialysis patients in a double-blinded study.16 Polidocanol is a non-ionicsurfactant with both local anesthetic properties and moisturizing effects. A combination of 5% urea and 3% polidocanol was found to significantly reduce pruritus in patients with atopic dermatitis, contact dermatitis, and psoriasis.17
Topical Salicylic Acid
Topical salicylic acid, a cyclooxygenase inhibitor, has been shown to significantly reduce pruritus in patients with lichen simplex chronicus, possibly due to their inhibitory effects on prostanoids.18,19 Of note, oral salicylates do not relieve pruritus except in polycythemia vera.
N-palmitoylethanolamine, a cannabinoid receptor CB2 agonist, has been incorporated into creams and shown to reduce pruritus reported in patients with atopic dermatitis, lichen simplex, prurigo nodularis, and chronic kidney disease-associated itching.20-22
With the exception of chronic urticaria, antihistamines have little effect on conditions associated with pruritus. Sedating (first generation) antihistamines may have a role via their soporific effects on nocturnal pruritus, but in the elderly caution must be taken to avoid causing excessive drowsiness.23
The serotonin-norepinephrine re-uptake inhibitor (SNRI), mirtazapine, has been reported to relieve itch in patients with advanced cancers (e.g., leukemia and lymphoma, including cutaneous lymphoma), chronic kidney disease, and cholestasis.24-26 Mirtazapine may also be especially useful for the treatment of nocturnal pruritus.25 Additionally, selective serotonin re-uptake inhibitors (SSRIs) may have antipruritic effects. The SSRIs, paroxetine and fluvoxamine, have been shown to reduce chronic pruritus, with the most favorable responses seen in patients with pruritus due to atopic dermatitis, systemic lymphoma, and solid carcinoma; whilst sertraline has been shown to be an effective treatment for pruritus associated with chronic liver disease.27,28
Although the antiprurituc mechanism of antidepressants is unclear, medications interfering with neuronal re-uptake of neurotransmitters, such as serotonin and norepinephrine, may act through the cerebral cortex to reduce the perception of pruritus.29 Antidepressants may be particularly useful in elderly patients with psychogenic causes of pruritus. Of note, it may be prudent to start with lower doses of antidepressants in the elderly and then taper up cautiously to avoid the significant side-effects associated with these medications.
Opioid Agonists and Antagonists
An imbalance of the endogenous opioidergic system may have a role to play in the pathophysiology of pruritus. Itch is induced by both μ-opioid receptor agonists and κ-opioid receptor antagonists, while μ-receptor antagonists and κ-receptor agonists can reduce it. Studies have shown the antipuritic effects of μ-opioid receptor antagonists, such as naltrexone (in patients with cholestasis, end-stage renal disease, burns, and atopic dermatitis) and nalmefene (in patients with cholestasis, atopic dermatitis, and urticaria).30-34
|Drug Class||Medication & Suggested Dose||Notes/Adverse Effects|
|Sedating Antihistamines||Hydroxyzine: start at 25 mg daily and taper up to 75 mg qd as tolerated||No direct effect on pruritus except in urticaria; sedating antihistamines are useful through their soporific effects; beware of excessive drowsiness especially in the elderly|
|Antidepressants||Recommend starting at low doses in the elderly and tapering up to avoid side-effects|
|SNRIs||Mirtazapine 7.5-15 mg PO qhs||May cause increased weight, appetite, and somnolence|
|SSRIs||Paroxetine 10-40 mg PO qd
Fluvoxamine 25-150 mg PO qd
Sertraline 75-100 mg PO qd
Useful in cholestatic pruritus
|μ-opioid Receptor Antagonists||Naltrexone 25-50 mg PO qd||Useful in patients with cholestatic and CKD-associated pruritus; may cause nausea, vomiting, and drowsiness; recommend use in the elderly under specialist supervision|
|κ-opioid Receptor Agonists||Butorphanol 1-4 mg intranasally qd||Useful in nocturnal and intractable pruritus; may cause nausea, vomiting, and drowsiness; recommend use in the elderly under specialist supervision|
|Nalfurafine 2.5-5 ìg PO qd||Useful in CKD-associated pruritus; may cause insomnia; approved in Japan only; recommend use in the elderly under specialist supervision|
|Neuroleptics||Gabapentin 100-2400 mg PO qd||Useful in neuropathic pruritus; start at low doses and taper up in the elderly; may cause drowsiness, weight gain, and leg swelling|
|Pregabalin 25-150 mg PO qd||Start at low doses and taper up in the elderly; should not be stopped abruptly due to the risk of withdrawal symptoms|
|Table 2. Systemic treatments of pruritus||CKD = Chronic kidney disease|
The κ-opioid receptor agonists, butorphanol and nalfurafine, appear to have an antipruritic effect in patients with chronic intractable itch and chronic kidney disease, respectively.35,36 Due to the potential adverse effects associated with opioid agonists and antagonist, treatment is advisable under specialist supervision and at lower initial doses, especially in the elderly.
The neuroleptics, gabapentin and pregablin, are structural analogs of the neurotransmitter γ-aminobutyric acid (GABA). The exact mechanisms of their antipruritic effects are not clear, but they may be related to inhibition of central itch pathways. Neuroleptics may be particularly useful in the elderly for neuropathic pruritus related to conditions such as brachioradial pruritus, postherpetic neuralgia, and notalgia paresthetica.6,14 Gabapentin has been shown to reduce pruritus in patients with chronic kidney disease and lymphoma, but treatment can actually worsen the itching in patients with cholestasis.26,37 Of note, it has been suggested that using a lower dose of gabapentin with slow upward titration may reduce the risk of gabapentin-induced neurotoxicity and/or
coma in patients with reduced renal function, a problem that may be more prevalent in the elderly.38 Additionally, treatment with pregabalin should not be stopped abruptly due to the risk of withdrawal symptoms.39
Ultraviolet A (UVA), broadband ultraviolet B (BB-UVB), and narrowband UVB (NB-UVB)-based phototherapies have been used for over three decades to treat various pruritic dermatoses. This mode of treatment may be particularly suitable in the elderly as it avoids the risk of adverse drug reactions (although the risk of phototoxicity is increased) and overcomes challenges such as physical and cognitive limitations that can lead to noncompliance.
The multitude of variables that come with advanced age means that the management of pruritus in the elderly continues to pose a particular diagnostic and therapeutic challenge. Physical and cognitive limitations, multiple comorbid conditions, and polypharmacy are some aspects that can influence choice of treatment in this age group. Management of pruritus in the elderly must take an individualistically tailored approach with consideration of the patient’s general health, the severity of symptoms, and the adverse effects of treatment.
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- Fleischer AB, Jr. Pruritus in the elderly: management by senior dermatologists. J Am Acad Dermatol 28(4):603-9 (1993 Apr).
- Ward JR, Bernhard JD. Willan’s itch and other causes of pruritus in the elderly. Int J Dermatol 44(4):267-73 (2005 Apr).
- Wang H, Yosipovitch G. New insights into the pathophysiology and treatment of chronic itch in patients with end-stage renal disease, chronic liver disease, and lymphoma. Int J Dermatol 49(1):1-11 (2010 Jan).
- Yosipovitch G, Samuel LS. Neuropathic and psychogenic itch. Dermatol Ther 21(1):32-41 (2008 Jan-Feb).
- van Os-Medendorp H, Ros WJ, Eland-de Kok PC, et al. Effectiveness of the nursing programme ‘Coping with itch’: a randomized controlled study in adults with chronic pruritic skin disease. Br J Dermatol 156(6):1235-44 (2007 Jun).
- Steinhoff M, Neisius U, Ikoma A, et al. Proteinase-activated receptor-2 mediates itch: a novel pathway for pruritus in human skin. J Neurosci 16;23(15):6176-80 (2003 Jul).
- Yosipovitch G, Papoiu AD. What causes itch in atopic dermatitis? Curr Allergy Asthma Rep 8(4):306-11 (2008 Jul).
- Dykes PJ, Marks R. An appraisal of the methods used in the assessment of atrophy from topical corticosteroids. Br J Dermatol 101(5):599-609 (1979 Nov).
- Stander S, Schurmeyer-Horst F, Luger TA, et al. Treatment of pruritic diseases with topical calcineurin inhibitors. Ther Clin Risk Manag 2(2):213-8 (2006 Jun).
- Patel T, Ishiuji Y, Yosipovitch G. Menthol: a refreshing look at this ancient compound. J Am Acad Dermatol 57(5):873-8 (2007 Nov).
- Papoiu AD, Yosipovitch G. Topical capsaicin. The fire of a ‘hot’ medicine is reignited. Expert Opin Pharmacother 11(8):1359-71 (2010 Jun).
- Wood GJ, Akiyama T, Carstens E, et al. An insatiable itch. J Pain 10(8):792-7 (2009 Aug).
- Imamachi N, Park GH, Lee H, et al. TRPV1-expressing primary afferents generate behavioral responses to pruritogens via multiple mechanisms. Proc Natl Acad Sci U S A 106(27):11330-5 (2009 Jul 7).
- Young TA, Patel TS, Camacho F, et al. A pramoxine-based anti-itch lotion is more effective than a control lotion for the treatment of uremic pruritus in adult hemodialysis patients. J Dermatolog Treat 20(2):76-81 (2009).
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- Yosipovitch G, Sugeng MW, Chan YH, et al. The effect of topically applied aspirin on localized circumscribed neurodermatitis. J Am Acad Dermatol 45(6):910-3 (2001 Dec).
- Andoh T, Nishikawa Y, Yamaguchi-Miyamoto T, et al. Thromboxane A2 induces itch-associated responses through TP receptors in the skin in mice. J Invest Dermatol 127(8):2042-7 (2007 Aug).
- Szepietowski JC, Szepietowski T, Reich A. Efficacy and tolerance of the cream containing structured physiological lipids with endocannabinoids in the treatment of uremic pruritus: a preliminary study. Acta Dermatovenerol Croat 13(2):97-103 (2005).
- Eberlein B, Eicke C, Reinhardt HW, et al. Adjuvant treatment of atopic eczema: assessment of an emollient containing N-palmitoylethanolamine (ATOPA study). J Eur Acad Dermatol Venereol 22(1):73-82 (2008 Jan).
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- Patel T, Ishiuji Y, Yosipovitch G. Nocturnal itch: why do we itch at night? Acta Derm Venereol 87(4):295-8 (2007).
- Davis MP, Frandsen JL, Walsh D, et al. Mirtazapine for pruritus. J Pain Symptom Manage 25(3):288-91 (2003 Mar).
- Hundley JL, Yosipovitch G. Mirtazapine for reducing nocturnal itch in patients with chronic pruritus: a pilot study. J Am Acad Dermatol 50(6):889-91 (2004 Jun).
- Demierre MF, Taverna J. Mirtazapine and gabapentin for reducing pruritus in cutaneous T-cell lymphoma. J Am Acad Dermatol 55(3):543-4 (2006 Sep).
- Stander S, Bockenholt B, Schurmeyer-Horst F, et al. Treatment of chronic pruritus with the selective serotonin re-uptake inhibitors paroxetine and fluvoxamine: results of an open-labelled, two-arm proof-of-concept study. Acta Derm Venereol 89(1):45-51 (2009).
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- Kumagai H, Ebata T, Takamori K, et al. Effect of a novel kappa-receptor agonist, nalfurafine hydrochloride, on severe itch in 337 haemodialysis patients: a phase III, randomized, double-blind, placebo-controlled study. Nephrol Dial Transplant 25(4):1251-7 (2010 Apr).
- Bergasa NV, McGee M, Ginsburg IH, et al. Gabapentin in patients with the pruritus of cholestasis: a double-blind, randomized, placebo-controlled trial. Hepatology 44(5):1317-23 (2006 Nov).
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