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Table of contents
- Itch : mechanisms and treatment
- Itch : mechanisms and treatment (Book, ) [leondumoulin.nl]
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Second-generation antihistamines are preferred for treatment of histaminergic forms of itch such as chronic urticaria owing to their reduced anticholinergic effects [ 93 ]. Loratadine, however, has the most anticholinergic effects of all the second-generation antihistamines, and should be avoided in the elderly [ 88 ]. TCAs such as amitriptyline and doxepin are also recommended against because of their anticholinergic effects as well as orthostatic hypotension [ 91 ].
TCAs have been shown to be effective in the treatment of nocturnal itch and psychogenic itch [ 75 ]. Alternatives for the treatment include antidepressants with a more favorable side effect profile in the elderly, such as the selective serotonin reuptake inhibitors SSRIs and serotonin and norepinephrine reuptake inhibitors SNRIs as well as behavioral therapy or psychotherapy [ 75 ].
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The SSRIs paroxetine, fluvoxamine, and sertraline have been shown to have antipruritic effects in AD, lymphoma, and cholestatic pruritus [ 94 , 95 , 96 ]. However, the SSRIs and SNRIs are not without their potential adverse effects in the elderly, as both classes were recently added to the AGS Beers Criteria to be avoided in those with a history of falls or fractures, as a result of evidence increased risk of hip fractures [ 97 ]. In addition, paroxetine has the greatest anticholinergic properties of that class of medications and therefore would not be the SSRI of choice for treatment in an elderly patient [ 91 ].
Mirtazapine, an antidepressant that blocks adrenergic alpha 2 receptors and 5-HT 2 receptors has shown effectiveness at low doses in relieving nocturnal itch. This medication in low doses of 7. Corticosteroids are used frequently in inflammatory and immune-mediated dermatologic conditions that cause itch. The known adverse effects of systemic include hypertension, hyperglycemia, osteoporosis, and myopathy. In addition, caution must be taken to avoid the use of corticosteroids in combination with the non-steroidal anti-inflammatories NSAIDs in the elderly, as this increases the risk of peptic ulcers and gastrointestinal bleeding [ 91 ].
Other pan-T cell immunosuppressants such as cyclosporine, which has many side effects as high blood pressure, renal damage, and systemic infections, should be avoided. Low-dose methotrexate is a safer alternative that can be effective for itch caused by AD, psoriasis, BP, and urticaria [ 99 ]. Because of renal clearance, dose adjustments may be required in the elderly or those with kidney disease.
Potential adverse effects such as sedation and ataxia are of concern in elderly patients with limited baseline mobility or cognitive functioning [ ]. Opioids are a well-described cause of medication-induced pruritus and do so through activation of central mu-opioid receptors [ ]. Medications that antagonize the mu-opioid receptor, such as naloxone, naltrexone, or nalmefene, have been demonstrated to be effective in reducing itch in chronic urticaria, AD, PN as well as cholestatic and uremic itch [ ].
Side effects including nausea, vomiting, diarrhea, dizziness, and fatigue and the potential for hepatic injury at high doses necessitate caution with the use in the elderly [ ]. In contrast, activation of kappa-opioid receptors inhibits pruritus. Butorphanol, a kappa-opioid agonist with some mu-opioid antagonist properties, has been shown in case series to effectively reduce itch due to PN, cholestasis, uremic itch, and idiopathic pruritus in elderly patients [ , ].
Nalfurafine, which has a similar mechanism of action, has been demonstrated in randomized controlled trials RCTs to reduce uremic itch and cholestatic itch and is currently only used clinically in Japan [ ]. Side effects have been noted to be minimal with insomnia most commonly reported followed by constipation and somnolence [ ]. New kappa-opioid agonists in the pipeline such as nalbuphine and CR show promise in early phase trials for uremic itch with a favorable safety profile [ , , ].
Dupilumab, a monoclonal antibody targeting the receptor for IL-4, has been shown in large RCTs to reduce symptoms and improve quality of life in those with moderate to severe AD [ , ]. The average age of participants in these trials was under 50, providing little evidence of efficacy in the elder population. We have gained clinical experience using this drug in older patients with success, including a year-old with itch refractory to other treatments Yosipovitch, unpublished data.
Itch : mechanisms and treatment
Adverse effects have not been specifically outlined in the elderly, but in the general adult population they include conjunctivitis, headache, and injection site reaction. There has been no demonstrated increased risk of secondary infections such as herpes viral infections or urinary tract infections that would be of particular concern when prescribing to the elder patient [ ]. Several additional biologic therapies including targets of IL and JAK show promise in early phase trials for their antipruritic properties particularly for AD, PN, and chronic idiopathic pruritus [ , ].
JAK inhibitors such as tofacitinib have adverse effects that should be strongly considered when used in the elderly including increased risk of herpes and other infections [ ]. NK1 is the receptor for substance P, and antagonist medications such as aprepitant and serlopitant have been shown to be effective in reducing itch of various etiologies, including malignancy, ESRD, idiopathic itch, and PN [ , ]. The relatively mild adverse effect profile of aprepitant has been demonstrated in several RCTs for use in other disease states such as depression and chemotherapy-induced nausea [ ].
However, aprepitant is a known inducer of CYP3A4 and therefore has the potential for many drug—drug interactions [ ]. In one retrospective study, Bulur et al. Known risks of phototherapy include an erythematous sunburn reaction, aging of the skin, increased risk for non-melanoma skin cancer, and a paradoxical induction of itch if phototherapy doses are too high [ ].
Despite concerns of potential adverse effects due to age-related barrier and immune function, the minimal dose to cause erythema has not been shown to differ significantly between older and younger populations and adverse effects are reported at comparable rates [ , ]. However, at least one study found that if erythema was elicited by phototherapy, the intensity was significantly increased in the elderly [ ].
Consideration for low doses should be made for patients with high cumulative sun exposure or history of skin cancer. Also of note, some frequently used medications i. Chronic itch is a common symptom in the elderly population and may be due to age-related changes in the skin, primary dermatologic conditions, systemic disease, neuropathic diseases, or medications. Determining the underlying cause of chronic itch is necessary for appropriate treatment.
Because of medical co-morbidities, differential pharmacokinetics, polypharmacy, and potential for adverse reactions in the elderly, caution must be taken with certain medical therapies for chronic itch in this population. Dermatological problems in geriatric patients: a hospital based study. Nepal Med Coll J.
The prevalence of skin diseases in the elderly: analysis of geriatric patients. Int J Dermatol. European S2k guideline on chronic pruritus. Acta Derm Venereol. The impact of chronic urticaria on the quality of life. Br J Dermatol.
Itch : mechanisms and treatment (Book, ) [leondumoulin.nl]
The prevalence and clinical characteristics of pruritus among patients with extensive psoriasis. A questionnaire for the assessment of pruritus: validation in uremic patients. The impact of pruritus on quality of life: the skin equivalent of pain. Arch Dermatol. Itch prevalence and characteristics in a Hispanic geriatric population: a comprehensive study using a standardized itch questionnaire. Pruritus in the older patient: a clinical review.
Retrospective analysis of data from an itch center: integrating validated tools in the electronic health record. J Am Acad Dermatol. Chronic pruritus of unknown origin CPUO : uniform nomenclature and diagnosis as a pathway to standardized understanding and treatment.
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Prevalence and risk factors for xerosis in the elderly: a cross-sectional epidemiological study in primary care. Ali SM, Yosipovitch G. Skin pH: from basic science to basic skin care. Protease-activated receptors and itch. Handb Exp Pharmacol. Acid and neutral sphingomyelinase, ceramide synthase, and acid ceramidase activities in cutaneous aging.
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Exp Dermatol. Age-related changes in skin barrier function - quantitative evaluation of female subjects. Int J Cosmet Sci. Aquaporin-3 gene and protein expression in sun-protected human skin decreases with skin ageing. Australas J Dermatol. Immunosenescence in aging: between immune cells depletion and cytokines up-regulation. Clin Mol Allergy. Immunological and non-immunological mechanisms of allergic diseases in the elderly: biological and clinical characteristics. Immun Ageing. Immunological pathogenesis of main age-related diseases and frailty: role of immunosenescence. Eur Geriatr Med.