US Pharm. 2013;38(12):18-20.
In the United States, gastrointestinal
disorders in geriatric patients account for a significant portion of
clinician visits, inpatient hospitalizations, and healthcare
expenditures.1 Inflammatory bowel disease (IBD), a group of
debilitating conditions of which the vast majority of cases are composed
of ulcerative colitis (UC) and Crohn’s disease (CD), is found with
increasing frequency in the elderly. This may be partially attributed to
an increasing number of IBD patients currently living into old age.2 This article will review treatment issues and briefly discuss the relevance of vitamin D in IBD.
IBD affects up to 0.5% of the population in developed countries and an increasing proportion in developing nations.3-5 These conditions are most prevalent in Western countries and in areas of northern latitude.6,7
For example, the incidence and prevalence of IBD are higher in northern
Europe, North America, Australia, and New Zealand than in Asia.3,4,8,9
Along those lines, the incidence of IBD in the Indian subcontinent is
low; however, migrants to developed countries located at northern
latitudes have a greatly increased risk of IBD.10 Furthermore, the onset of UC and exacerbations of CD are noted to peak in winter months in the Northern Hemisphere.11,12 The highest reported prevalence rates of IBD are in Scandinavia, Great Britain, and North America.6,7 The physiological activity of vitamin D is thought to be related to these observations. (See below, Vitamin D Deficiency in IBD.)
Although IBD affects both genders
equally, some studies indicate that more women suffer from CD, whereas
more males suffer from UC.7 While onset of IBD is more common
in early adulthood, epidemiologic evidence suggests a bimodal
distribution of the age of onset of both UC and CD; peak incidence
occurs in the second and third decades and a late-onset minor peak
between 60 and 80 years.1,13-15 Notably in the elderly
population, there are challenges in diagnosis of gastrointestinal (GI)
disorders that go beyond those of other patients. These include 1)
comorbid illnesses such as dementia and depression that may impair
communication between the patient and the caregiver; 2) medications,
such that therapeutic and adverse effects may cloud the clinical picture
in seniors, in whom polypharmacy is common; and 3) intestinal symptoms
in the elderly that may be manifestations of other diseases.1
Etiology, Underlying Pathogenesis, and Complications
While the exact etiology of UC and CD is
not known, both conditions are believed to be caused by similar factors.
Infectious factors such as viruses (e.g., in measles), protozoans,
mycobacteria (e.g., Mycobacterium paratuberculosis), and other bacteria (e.g., Chlamydia trachomatis, Escherichia coli) are all suspect agents.16,17
Genetic factors also predispose patients to IBD, especially to CD.
Characterized by a tendency for immune activation—both autoimmune and
nonautoimmune—and inflammation, IBD is associated with a dysregulated
mucosal immune response to intestinal microorganisms in a genetically
In addition to intestinal complications,
the IBD patient is at increased risk of systemic immune-related
phenomena such as arthritis, nutritional deficiencies related to
malabsorption of vitamin B12 and folic acid, anemia secondary
to blood loss from the GI tract, and bone disease, of which
osteoporosis and fractures are of particular concern.18 While
psychological factors (e.g., stress, emotional or physical trauma) are
thought overall not to be an etiological factor, changes in mental
health appear to potentially correlate with remissions and
exacerbations, particularly with regard to UC.15
Ongoing Inflammation: Risk of Colon Cancer
In patients with long-standing IBD, the
risk of colon cancer is a significant complication that appears to be
related to the degree of ongoing inflammation.1 Risk
increases substantially after 8 to 10 years of disease; when
appropriate, surveillance for colon cancer includes annual colonoscopy
with random mucosal biopsies for observation of early or advanced
The goals of treatment of IBD are 1)
resolution of acute inflammation and complications, such as fistulas or
abscesses; 2) alleviation of systemic manifestations like arthritis; 3)
maintenance of remission; and 4) in certain cases, palliation or cure
with surgery.15 Although the evaluation of IBD severity is
difficult due to the largely subjective nature of the assessment, more
objective measures, disease rating scales, and indices have been
developed, including those that assess quality of life (see Reference
15). Selected agents used in treating IBD can be found in TABLE 1.
Of note, there is a considerable difference between the goals of, and
approach to treatment for, UC and CD; for detailed discussions of IBD
medication therapy, including algorithm treatment approaches and
specific dosing guidelines, consult References 15 and 19. In order to
treat these diseases properly, realistic therapeutic goals for each
individual must be conceptualized by the clinician and ideally should
include collaboration with the patient to address issues including
quality of life and medication (TABLE 1) risks versus benefits.
Selected Tips Regarding Drug Therapy in the Elderly
Intolerance of drug therapy often limits
the usefulness of drugs that treat IBD. Adverse effects may be
significant in some cases, thus requiring discontinuation of the
therapy. Some of the nuances of IBD therapy are discussed below,
focusing on the elderly, to encourage the tailoring of the medication
regimen to the individual in conjunction with ongoing assessment (e.g.,
history and physical), close monitoring (e.g., selected laboratory
tests), and evaluation of therapeutic outcomes.
Avoiding NSAIDs: Reports
have indicated that NSAIDs may trigger IBD occurrence or trigger
exacerbation of underlying IBD; if possible, their use should be
avoided.15,20,21 The mechanism by which this occurs is
thought to be inhibition of prostaglandin production via cyclooxygenase
inhibition that may impair mucosal barrier protection. If the benefit of
treatment (e.g., of patients with symptomatic arthritis) outweighs the
potential risk of IBD flare, the use of NSAIDs may be warranted in some
patients.21 Of note, the elderly are a high-risk population
for adverse effects from NSAIDs; up to 60% of elderly people can develop
peptic ulceration and/or hemorrhage asymptomatically.19
Unlike other sulfonamides, sulfasalazine is not absorbed when
administered orally or as a suppository and is, therefore, reserved for
the treatment of chronic IBD. Of note, it is intestinal flora that
split sulfasalazine into two components: 5-aminosalicylate, which exerts
an anti-inflammatory effect, and sulfapyridine, which can lead to
toxicity in patients who are slow acetylators, whereby it precipitates
at neutral or acidic pH, causing crystaluria (stone formation).22
Nephrotoxicity may develop secondary to crystaluria; preventing this
adverse effect requires adequate hydration and alkalinization of urine.22 Patients receiving sulfasalazine should receive oral folic acid supplementation to prevent anemia secondary to malabsorption.15
Transient warfarin potentiation occurs
with concomitant sulfasalazine use owing to displacement of warfarin
from binding sites on serum albumin; free methotrexate levels may be
increased because of displacement as well.22 Other potential
problems associated with sulfasalazine are hypersensitivity reactions
such as rashes, angioedema, and Stevens-Johnson syndrome; in order to
direct appropriate therapy, it is of paramount importance to investigate
a report of a previous sulfa allergy with regard to a description of
the reaction.22,23 Granulocytopenia, thrombocytopenia, and
hemolytic anemia (i.e., in patients with glucose 6-phosphate
dehydrogenase deficiency) can occur.22 Since sulfonamides
condense with formaldehyde, sulfasalazine is contraindicated in patients
who receive methenamine for urinary tract infections.22
80% to 90% of patients who are intolerant to sulfasalazine’s adverse
effects will tolerate oral mesalamine derivatives.24 With regard to rectal suppositories, the elderly may have difficulty administering and retaining this dosage form.19 In light of age-related renal function decline, serum creatinine should be monitored often during therapy.19
systemic corticosteroids are effective in moderate-to-severe active UC
and CD, high doses must often be used for extended periods; thus, their
use confers a higher risk of complications in the elderly, including
accelerated bone loss and fractures, hypertension, and glucose
intolerance.1,15 Use of systemic corticosteroids in geriatric
patients should involve the lowest possible dosage, and for the
shortest possible time. For long-term use, bone mineral density should
be monitored and fracture prevention strategies should be instituted (TABLE 2).19,25 Corticosteroids are not effective as maintenance treatment in either UC or CD.15
Immunomodulator and Immunosuppressive Agents: These
drugs are associated with an increased risk for toxicity in the
elderly. Recommended dosages should be reduced when initiating therapy
in geriatric patients because of possible decreased metabolism, reduced
renal function, and presence of comorbidity-drug interactions and
tumor necrosis factor alpha (TNF-α) inhibitors predispose patients to
development of serious infections; studies indicated that the elderly
have an increased incidence of infection and malignancy compared to
younger adults under 65 years of age.19 The use of
natalizumab, a novel biological agent, is associated with the
development of progressive multifocal leukoencephalopathy.26
In light of the higher incidence of infections and malignancies in the
geriatric population, caution and close monitoring are advised when
these agents are used in the elderly.19 In addition, elderly
patients with a history of heart failure may be at risk for
exacerbation. Infliximab is contraindicated for individuals with New
York Heart Association (NYHA) Class III-IV heart failure; caution is
advised in those with congestive hear failure or NYHA Class I-II.19,26
Vitamin D Deficiency in IBD
Vitamin D deficiency is more common in adults and children with IBD (especially CD), as compared with healthy controls, and correlates with a poorer health-related quality of life.27-32
Factors such as malabsorption (i.e., secondary to mucosal disease or
surgical resection) and reduced sunlight exposure, physical activity,
and dietary intake are likely to contribute to this finding.18
not specifically studied in patients with IBD, it is thought that an
active inflammatory state may cause a reduction in total 25(OH)D3 levels, owing to reduced hepatic
production of vitamin D–binding protein.33
Garg and colleagues point out that the relationship between IBD and the
vitamin D axis appears to be a multi-faceted one involving the ongoing
maintenance of musculoskeletal health (TABLE 2) and possibly the
control of disease-related activity via immunomodulation, and
modification of the risk of IBD-associated malignancy.18 A
review of the role of vitamin D in bone health, immune regulation, and
cancer prevention in IBD is available at
While onset of IBD is common in young
adults, it also is found with increasing frequency in the elderly.
Currently, there is a greater and better variety of agents to treat
patients with IBD for both acute conditions and remission maintenance.
Medication regimens for senior IBD patients, based on the nuances of
these therapies, require careful and appropriate geriatric dosing,
monitoring, and ongoing assessment.
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