In this study we analyzed and we compared clinical presentation, disease course, complications and therapeutic strategies of UC in a group of patients who were diagnosed with UC during old age (≥ 65 years) and in a group of patients who were diagnosed with UC between 40 and 64 years. The study is prospective observational, and the two groups are homogeneous for type of disease, sex and age at diagnosis.
Among the patients followed at our IBD outpatient clinic (Gastroenterology Unit, Spedali Civili Hospital), from 1° January 2000 to 30 June 2019 all new diagnoses of UC were considered. The total study number of patients was 188, 94 elderly and 94 adults. A median follow up of 7 years was reached.
Family history, smoking habits and NSAIDs use are confirmed as risk factors for UC. In fact, a family history for UC (< 10%) was found in both groups among 1st grade relatives, as we can see in the EPIMAD register (IBD register in North-western Italy). In line with previous studies [12], non smokers or ex smokers are prevalent in UC (p 0.002).
Time between symptoms onset and UC diagnosis is similar between the two groups, with a median value of 6 months. The most common misdiagnosis was diverticular disease, probably because the prevalence of diverticula was significantly higher in the elderly (p < 0.0005).
Compared to previous studies [13,14,15], diagnostic delay was higher in the elderly.
Data about clinical presentation and disease extent are similar to the ones we find in previous studies [15,16,17,18,19,20,21,22], with differences between elderly and adults not statistically significant.
UC clinical presentation was similar in the two groups, except for abdominal pain, which was more common in the elderly. At UC diagnosis, left colitis was more common in the elderly, while proctitis was less common (p 0.001). During follow up, 13% of patients had an extension of the disease [15, 17, 20,21,22].
Data about extraintestinal manifestations are similar to the ones we find in earlier studies [13, 14]. Although at the time of diagnosis the number of patients with extraintestinal manifestations was similar in both groups, during follow up they were less common in the elderly (p 0.06). There may be several reasons for these differences.
Most of IBD extraintestinal manifestations involve joints. Joint pain in the elderly may be classified as a pain due to arthrosis; patients may not refer this kind of pain, because they consider it as a part of geriatric disease. Moreover, most of extraintestinal manifestation, in particular the arthritic ones, develop during disease exacerbation. Disease relapses are less frequent in the elderly and this could explain why extraintestinal manifestations develop less frequently.
According to previous studies [18, 23, 24], many differences were found also in therapeutic strategies. Therapy for induction of remission was similar in the two groups, with a similar use of mesalamine and steroids [25].
Many differences were found for surgery. The use of surgery for the induction of remission was similar in the two groups, while its use during follow up was much more frequent in the elderly (p 0.02). Thus, surgery is performed more frequently in the elderly. This may be due to limitations for some medical therapies during geriatric age. In fact, the number of patients who received immunomodulating therapy was significantly lower [19, 26,27,28,29].
Limitations in medical therapy are due to multimorbidity and polypharmacy typical of geriatric age [30]. In fact, at the time of diagnosis elderly patients have a comorbidity and severity index significantly higher compared to adult population (p < 0,0005) and, subsequently, a higher number of drugs taken (p < 0.005). At the time of diagnosis, many elderly patients had a history of cancer, myocardial infarction and heart failure. These diseases contraindicate a therapy with immunosuppressant and antiTNFα.
As widely reported in literature [24, 31,32,33,34], disease-related complications and therapy-related complications are more frequent in the elderly. Frequency of intestinal complications, infectious complication and side effects of steroid therapy is higher, while frequency of adverse drug reactions is similar in the two groups, if we exclude the ones related to biological therapy.
The most frequent intestinal complications were stenosis. However, they all take place in patients who also have a concomitant diverticular disease. The most frequent infectious complications were pneumonia, sepsis, complicated UTI, while the most relevant side effects of steroid therapy were diabetes, osteoporosis and hypertension [35,36,37,38].
Multimorbidity and polypharmacy may be relevant for the development of these complications. Intestinal complications may be due to a poor control of the disease deriving from polypharmacy, which determines, in the first place, a lower adherence to therapy. This may be worsened by cognitive impairment [39, 40], which was found in 18% of patients at the end of follow up. Secondly, even when the adherence to therapy is adequate, elderly patients have alterations in all levels of pharmacokinetics, with altered absorption (achlorhydria), distribution (hypoalbuminemia and dehydration), metabolism (enzyme induction) and excretion (kidney failure). These elements may create interactions which are often unknown or not characterisable, and may determine a major or minor drug activity with intraindividual and interindividual variability.
Alternatively, if we consider the major frequency of side effects related to steroid therapy, the reasons are similar to the ones previously described for intestinal complications. Moreover, this kind of therapy may worsen other conditions which are frequent during geriatric age, such as osteoporosis, diabetes, hypertension, insomnia and major infectious risk, which can be also related to the senescence immune system of the elderly.
Finally, considering incident pathologies during follow up, we can find more frequently cognitive impairment, DVT/pulmonary embolism, myocardial infarction, stoke and cancer, both intestinal and non intestinal. Moreover, mortality is significantly higher during geriatric age (20% vs 2%, p < 0.0005). (Fig. 4)