People 65 years old or more are the fastest growing segment of the population in the developed countries. By 2030, it is estimated that this group will comprise about 20% of the total population, and among elderly persons, the percentage of patients aged above 80 years will increase disproportionately. The prevalence of allergic diseases, in the elderly is estimated around 5-10% [
1,
2]. Although allergic conditions are often thought of as childhood disorders, the disease often persists into older age and can occasionally make its initial appearance in the elderly.
Specific issues that arise when investigating allergies in the elderly patients are several. First of all, the definition of older persons needs to be clarified in order to homogenize nomenclature when addressing this entity. Usually, the term older adults is applied to persons 65 years or older, since it takes into account not only the chronologic aspect of aging, but also the fact that around this is retirement age in many countries. Subclassification into several ranges after this age may take into account increasing frailty, comorbidities and dependence.
A number of factors in older subjects contribute to their risk for developing allergic related conditions. These include frailty, coexisting medical problems, memory issues and use of multiple prescribed and non prescribed medications [
3]. However, more studies should be designed so as to know the prevalence and particularities of allergy in the elderly since data in this field are scarce. Also, recruitment of older subjects into clinical trials is necessary to provide a reliable evidence base to facilitate the identification of safe and effective diagnostic and therapeutic methods for elderly patients with suspected allergic conditions.
Pharmacology in allergic elderly patients
The potential for drug interaction increases with age and with the number of drugs prescribed [
80]. The most important mechanisms for drug-drug interactions are the inhibition or induction of drug metabolism, and pharmacodynamic potentiation or antagonism. This is because the elderly have reduced homeostatic mechanisms, decreased renal function and a biotransformation in the liver may also play a role and are therefore particularly sensitive to, for example, the combined postural hypotensive or sedative effects of drugs [
81]. Strategies to avoid drug-drug interactions in the elderly include an appropriate alerting system in computers in general practice, exercising care in prescribing, monitoring patients regularly, paying special attention to institutionalised and frail elderly patients, auditing drug interactions and reporting drug interactions to the regulatory authorities.
When prescribing a treatment for AR in the elderly, the possibility of drug-drug interactions, and the impact of drug treatment on concomitant diseases should be taken into account. Nasal steroids, topical antihistamines and non-sedating antihistamines are particularly suited for management of AR in the elderly both for safety and efficacy. Clearance of leukotriene receptor antagonists is decreased in the elderly, and has the potential to interact with a wide range of drugs that inhibit or induce the CYP 3A4 or 2C9 systems [
34]. As a general rule, first-generation antihistamines should not be used for AR in the elderly due to risks of side effects and interactions with other medications [
82]. Topical and systemic decongestants should also be avoided because they may aggravate nasal dryness and cause systemic side effects such as confusion, difficulty in urination, irritability and aggravation of glaucoma. Non-pharmacologic treatment should include nasal lavage with isotonic sodium chloride for reducing nasal dryness and clearing thick mucus [
83].
Management of asthma in older patients seems suboptimal, and the use of inhaled corticosteroids is low, although they are probably the best maintenance therapy in most patients [
37,
84]. Nevertheless, medical evidence in this age group is very limited due to the systematic exclusions of elderly people, smokers or patients with concomitant COPD from trials, and subsequently guidelines derived from such evidence may not be fully applicable to older patients or those with several comorbidities. In the case of older asthmatics, all these issues should be carefully assessed when establishing management, as well as possible drug interactions, capability to use inhaler devices and patient preferences.
The use of long-acting β-adrenergic agonists (LABAs) has a synergic effect with inhaled corticosteroids. Although older patients with coronary disease may be more prone to adverse side effects, they are generally considered safe, but discontinuation should be considered when control of asthma is achieved [
85,
86]. Also short-acting β-adrenergic agonists can cause cardiotoxicity in case of overdosing. In some cases, the use of an anticholinergic aerosol could be a therapeutic option. Other alternative treatments such as leukotriene receptor antagonists, which may be useful in some aspirin sensitive patients, or theophylline, may be considered. Nevertheless, due to its narrow therapeutic window, careful monitoring is advised if theophylline is used. Influenza and pneumococcus immunization protect against these respiratory infections which are directly related to a significant number of asthma exacerbations, and should therefore be recommended in older asthmatics [
87].
Options for treatment of skin allergic disorders include topical and systemic drugs. Topical treatments may prevent major adverse effects. Cooling agents such as menthol, may decrease the intensity of itching by activation of low temperature receptors in the skin. Anaesthetics with formulations based on benzocaine or lidocaine are widely used, especially in neuropathic pruritus, but they can induce ACD and may induce side effects in the circulatory system [
88]. Antihistamines such as topical doxepine are effective in atopic and ACD. Other topical antihistamines may induce contact allergy [
89]. Capsaicin owes its antipruritic properties to desensitization of sensory nerve fibres and it has shown to be effective in nostalgia paraesthetica, prurigo nodularis and uremic pruritus [
88]. Topical corticosteroids have limited value in the treatment of pruritus; they might only be effective in inflammatory skin disorders. Calcineurin inhibitors are potent antipruritic drugs in patients with atopic dermatitis [
90]. N-palmitoylethanolamine, a cannabinoid receptor CB2 agonist, is a promising new compound that activates cannabinoid receptors in the skin and has shown to reduce pruritus in atopic dermatitis, lichen simplex, prurigo nodularis, and chronic kidney disease-associated itching [
91].
Systemic treatment options for pruritus include sedating antihistamines, antidepressants, μ- or κ-opioid receptor agonists and neuroleptics. Most of these drugs are not devoid of relevant side effects, such as drowsiness. Therefore it is usually recommended to start at low doses in the elderly and to taper up [
92]. UVB phototherapy is effective especially in uremic pruritus, cholestasic pruritus and HIV-associated pruritus [
93]. Psychotherapy is helpful in the treatment of somatoform pruritus or neurotic excoriations.
Atopic dermatitis, and all of the others forms of dermatitis that are recalcitrant to other therapies, can be treated with topical or systemic corticosteroids. If they are ineffective or adverse effects preclude the use of corticosteroids, treatment with calcineurin inhibitors, phototherapy, or systemic immunosuppressives such as cyclosporine could be used [
55].
Antihistamines
First-generation H1 receptor antagonists are lypophilic and therefore may cross the blood-brain barrier. Elderly persons may be at greater risk of adverse effects involving the CNS, such as confusion, sedation, dizziness, sleepiness or impaired cognitive function [
94]. It has been shown that diphenhydramine administration in older hospitalized patients over 70 years of age is associated with increased risk of cognitive decline compared with nonexposed patients [
95]. Because of the lack of specificity for the H1 receptor, first generation antihistamines also have additional dopaminergic, serotoninergic, muscarinic and cholinergic adverse effects [
96]. Thus, particularly in the elderly, there is a higher risk of urinary hesitancy, urinary retention, constipation, as well as arrhythmias, peripheral vasodilatation, postural hypotension or tachycardia. These side effects may lead to falls or aggravation of concomitant diseases such as prostatic hypertrophy, glaucoma and heart disease. In a recent study on the inappropriate drug use and mortality in community-dwelling elderly, first-generation antihistamines accounted for one of most frequent drugs prescribed although contraindicated [
97]. In the light of these findings, first-generation antihistamines should be prescribed with extreme caution in elderly patients.
Second-generation antihistamines have a lower capacity to cause CNS-related adverse effects as they have a low potential to cross the blood-brain barrier, and provide selective H1 blockade without anticholinergic or alpha-adrenoreceptor antagonist activity. Some second-generation antihistamines are metabolized by the cytochrome 450 enzyme system in their first pass through the liver, which may lead to drug-drug interactions or elevated plasma drug interactions in patients with liver dysfunction and others are excreted through the kidneys and dosage has to be adjusted according renal function [
82]. Second-generation oral H1 antihistamines potentially requiring a dose reduction in patients with hepatic dysfunction include cetirizine, ebastine, levocetirizine, and loratadine. Those potentially requiring a dose reduction in patients with renal dysfunction include cetirizine, ebastine, fexofenadine and levocetirizine [
98]. According to the studies of Affrime et al in healthy subjects, no dosage adjustment for desloratadine is required in the elderly [
99].
Corticosteroids
Topical and oral corticosteroids are particularly useful in the treatment of acute and delayed hypersensitivity diseases. However, they have adverse effects on many organ system, and these range from those that are not necessarily serious (e.g. cushingoid appearance), to those that are life-threatening (e.g. serious infections)[
100].
Some of these adverse effects may be aggravated in the elderly. Patients receiving prednisolone 5-40 mg/day for at least 1 year have a partial loss of explicit memory, and elderly patients may be more susceptible to memory impairment with less protracted treatment [
101].
The risk of developing diabetes mellitus is increased by more than two-fold in elderly patients who are newly initiated on oral corticosteroid therapy [
102]. An increased risk for peptic ulcer disease has been reported in corticosteroid users who were receiving NSAIDs concurrently, persons receiving NSAIDs and corticosteroids have a risk for peptic ulcer disease that is 15 times greater than that of nonusers of either drug [
103]. This finding is especially important in allergy practice because patients receiving oral corticosteroids are likely to be receiving NSAIDs as well, given that aspirin or other NSAIDs are among the most prescribed drugs in old age [
100].
Other frequent conditions of old age such as cataracts [
104] or osteoporosis [
105] have also been related to the use of systemic but also of high doses of inhaled corticosteroids, and should be borne in mind when treating allergic geriatric patients.
Specific immunotherapy in the elderly
Altered function of aged immune system is primarily associated with exposure to "new" antigenic challenges, as is the case for decreased efficient therapeutic value of vaccinations among the elderly population. While influenza vaccination has shown to reduce influenza-related mortality, current influenza vaccines have limited efficacy in elderly (17-53%) compared to vaccine efficacy in young adults (70-90%). To provide better protective measures for the increasingly aging population new and improved vaccines are needed. Currently, a variety of approaches are being explored to enhance the efficacy of influenza vaccines in the elderly, including the use of adjuvants, altering antigen dose and identifying the best routes of vaccine administration [
106]. There is not similar evidence with specific immunotherapy. There are few studies of use of this treatment in older adults.
Specific immunotherapy (SIT) is deemed the only treatment that can at least partly modify the natural course of the disease during its initial stages. Its use in elderly patients is still debated.
Injection SIT can be considered an effective therapeutic option in otherwise healthy elderly patients with a short disease duration whose symptoms cannot be adequately controlled by drug therapies alone [
107,
108]. One study also describes that sublingual immunotherapy (SLIT) reduces symptoms, drug consumption and the progression of the disease in both young and elderly subjects allergic to house-dust mites, with persistent rhinitis and mild bronchial asthma [
109].