Elderly Inflammatory Bowel Disease

　　The main pathogenic factors of elderly inflammatory bowel disease (IBD) include environment, genetics, infection, and immunity.

　　1. Environmental Factors

　　Epidemiological studies have found that the incidence of IBD varies greatly in different geographical locations and different periods; Asian immigrants and their descendants who migrate to Europe and America have an increased susceptibility to IBD. The incidence of IBD in African Americans has approached that of white Americans, while African blacks rarely suffer from IBD; the incidence of IBD in urban residents is higher than that in surrounding rural areas. This suggests that environment or lifestyle is closely related to IBD. Among the many environmental factors related to IBD such as smoking, oral contraceptives, events occurring in childhood, infection, and dietary factors, it is now clear that smoking can increase the risk of Crohn's disease (CD), while it has a protective effect on ulcerative colitis (UC).

　　2. Genetic Factors

　　The incidence of IBD shows significant differences among races; there is a phenomenon of family aggregation; the co-morbidity rate of IBD in monozygotic twins is higher than that in dizygotic twins; certain IBD patients often have diseases related to genetics and immune diseases with genetic susceptibility, all indicating that genetic factors play an important role in the pathogenesis of IBD. Early genetic research found that HLA genes are associated with IBD, but the results are not consistent. It is relatively certain that HLA-DR2, DR9, and DRB1*0103 alleles are associated with UC, and HLA-DR7 and DRB3*0301 alleles are associated with CD. In recent years, it has been found that certain cytokine gene polymorphisms are associated with IBD, such as the tumor necrosis factor gene (TNF-α-1031CD) associated with CD, and the interleukin-1 receptor antagonist gene associated with UC. Moreover, it has been found that the susceptibility genes for IBD are located on chromosomes 3, 7, 12, and 16. Among them, the NOD2/CARD15 gene located at the IBD1 locus on chromosome 16 has been the subject of much research in recent years. Research has confirmed that variations in this gene can increase the susceptibility to CD. The genetic study of IBD is not only crucial for elucidating the pathogenesis but may also have a breakthrough impact on the diagnosis and treatment of the disease. Current research shows that IBD is a polygenic disease with genetic heterogeneity (different people are caused by different genes).

　　3. Infection Factors

　　Due to the similarity of UC with infectious colitis caused by Salmonella, Shigella, or Amoeba, and CD with intestinal tuberculosis, people have been searching for intestinal bacteria or other microorganisms as infectious pathogens for many years. Research has found that the cellular and humoral immune responses of IBD patients to bacterial antigens are enhanced, bacterial retention is conducive to the occurrence of IBD, and fecal diversion can prevent the recurrence of CD. Antibiotics and probiotics are beneficial to some IBD patients, especially the recent discovery of animal models with immune deficiency caused by genetic engineering methods, which cannot induce intestinal lesions similar to IBD in a sterile state, suggesting that bacteria are related to the occurrence of IBD. However, to date, no specific microorganism pathogen has been found in bacteria, viruses, fungi, etc. that has a constant relationship with IBD. Therefore, it is currently considered that pathogenic microorganisms may be non-specific predisposing factors for the disease. Some people believe that IBD is caused by an abnormal immune response to the normal intestinal flora. As to whether there is a specific pathogenic microorganism in this disease and how it acts, further research is needed.

　　4. Immune Factors

　　The immune mechanism of IBD is one of the most active research fields in recent years, and the research progress has deepened our understanding of the immune-inflammatory process of IBD. The proposal of the immune mechanism is based on the fact that the disease often shows immune abnormalities, such as an increase in the number of intestinal mucosal immune cells, enhancement of local humoral or cellular immune activity, and various extra-intestinal manifestations in patients. The use of glucocorticoids or immunosuppressants can alleviate the disease. It is currently generally believed that IBD is caused by predisposing factors acting on susceptible individuals, triggering an exaggerated immune-inflammatory reaction of the intestinal mucosa related to genetics. The intestinal mucosal immune system plays an important role in the occurrence, development, and outcome of intestinal inflammation in IBD. Immune-inflammatory cells involved in intestinal immune-inflammatory reactions, such as neutrophils, macrophages, mast cells, lymphocytes, and natural killer cells, release antibodies, cytokines (interleukins, gamma interferon, TNF, TGF, etc.), and inflammatory mediators that cause inflammatory lesions and tissue damage. A large number of oxygen free radicals produced during the inflammatory process also have a damaging effect on the intestinal mucosa. In addition, non-immune cells in the intestines, such as epithelial cells and vascular endothelial cells, also participate in the inflammatory reaction and interact with local immune-inflammatory cells to exert their effects. There are many cytokines and mediators involved in immune-inflammatory reactions, and the interaction mechanisms between them are very complex, with some still unclear. The different manifestations of tissue damage depend on the expression and release of different cytokines. The synthesis of cytokines is mainly regulated by the gene transcription factors expressed by mucosal immune cells.

　　The immune response of UC and CD is different. CD has the characteristics of TH1 cell-mediated immune response (cellular immunity) and is a TH1-type response, while UC has the characteristics of antibody-mediated immune response (humoral immunity) and is a TH2-type response.

　　There are different opinions on the precipitating causes of the immune-inflammatory response in this disease. Some believe it may be food antigens or usually non-pathogenic intestinal symbiotic bacteria. Some studies have found that the colonic mucosa of patients with this disease may have abnormal epithelial cell structure and function and mucosal mucus layer, which increases the permeability of normal colonic mucosa, allowing normal colonic mucosa to pass through, which is generally harmless to normal people, symbiotic bacteria and food antigens can also enter the intestinal mucosa, thereby triggering a series of antigen-specific immune responses; the precipitating role of microbial pathogens has not been fully confirmed; some people also believe that this disease is an autoimmune disease. A series of autoantibodies against colonic epithelial cells, endothelial cells, neutrophils, and so on have been found in the serum of IBD patients, and some antibodies against bacterial, viral antigens, and food antigens have also been found. However, there is no direct evidence of pathogenicity caused by autoimmune reactions. In recent years, the reported autoantibodies, such as pANCA (perinuclear antineutrophil cytoplasmic antibodies), in the serum of UC patients have reached about 70%, while CD and normal people are usually below 20%. However, there is also no conclusive evidence of pathogenicity, so it is generally believed that pANCA may not participate in pathogenesis, may be the result of enteritis or a marker of genetic susceptibility, and its true meaning is yet to be elucidated.

　　The complications of elderly inflammatory bowel disease are mainly divided into two aspects.

　　1. Ulcerative colitis

　　Severe delayed-onset elderly ulcerative colitis patients are prone to complications of toxic megacolon. The mortality rate of toxic megacolon in patients over 40 years old is 30%, while in patients under 40 years old, the mortality rate is 5%. As for other extra-intestinal complications, there is no significant difference between early-onset elderly ulcerative colitis patients and delayed-onset ulcerative colitis patients in terms of joint and eye diseases, but the former have more frequent oral and skin ulcers.

　　In addition to proctitis, in general, the risk of colorectal cancer is related to the course of colitis; the longer the course, the higher the risk of concurrent tumor. For the risk of canceration in elderly ulcerative colitis, it is necessary to differentiate between late-onset ulcerative colitis and early-onset ulcerative colitis. The longer the history of early-onset ulcerative colitis, the higher the risk of colorectal cancer, but the relative risk of colorectal cancer (compared to non-ulcerative colitis patients of the same age) is smaller than that of young patients with a longer history of ulcerative colitis. The age-specific risk of late-onset ulcerative colitis patients is high, but the relative risk of colorectal cancer is smaller. For example, the relative risk of canceration in young people with severe colitis for 10 years is 20:1; for patients with colitis who developed after the age of 45 for 10 years, the relative risk of canceration is smaller, about 2:1.

　　2, Crohn's disease

　　There is no significant difference between the complications and extra-intestinal complications of elderly Crohn's disease and those of young Crohn's disease. However, the incidence of intestinal perforation in elderly Crohn's disease is higher than that in young Crohn's disease, and the incidence of abscesses and fistulas may also be high. The incidence of diverticulitis is high, and it often occurs in the intestinal lesion sites of Crohn's disease, which may be more prone to the occurrence of complications.

　　The incidence of colorectal cancer in patients with Crohn's disease colitis is slightly higher, but the relative risk is relatively small in general.

　　Most scholars believe that the main clinical manifestations and course of elderly ulcerative colitis are similar to those in young people, but diarrhea and weight loss are more prominent, while abdominal pain and rectal bleeding are rare. Zimmermann et al. reported that patients over 51 years old have more frequent diarrhea and a longer duration of clinical symptoms than patients aged 21 to 30, and the incidence of fulminant late-onset elderly ulcerative colitis is high, including some cases that developed before the age of 60 and those with delayed diagnosis leading to delayed treatment. The distribution of lesions in elderly ulcerative colitis is mostly in the distal rectum.

　　The clinical manifestations of late-onset Crohn's disease in the elderly are not much different from those in young people. The most common symptoms are diarrhea, weight loss, and abdominal pain, with other possible symptoms including rectal bleeding, fever, abdominal masses, perianal pain, and constipation. Woolrich and Korelitz believe that the most common clinical symptoms of elderly Crohn's disease are diarrhea, abdominal pain, and weight loss. Harper, based on patient gender and disease course matching, grouped them by age and found that the incidence of early bleeding in elderly Crohn's disease is high, while the incidence of abdominal masses and abdominal pain is low. Rectal bleeding and constipation are related to the location of the lesion in the colon. Stalnikowicz found that the diagnosis of elderly Crohn's disease is delayed, the misdiagnosis rate is increased, and the incidence of diarrhea, rectal bleeding, abscess formation, and complications is increased. Compared with young people, elderly Crohn's disease is more common in the colon, and it is more common in women. For example, rectal colitis in elderly Crohn's disease is more than 50%.

　　There is no special preventive method for elderly inflammatory bowel disease. It is important to actively treat underlying diseases. After being diagnosed, the following points should be noted to actively prevent complications.

　　1. Patients in the active phase should rest adequately.

　　2. Provide a low-residue, high-nutrition diet, and appropriately supplement folic acid, vitamin B12, and various vitamins and trace elements. Severe cases may require fasting.

　　3. In patients with concurrent infection, active anti-infection treatment is important, as gastrointestinal infections are a significant cause of disease and death. Bacteria, viruses, and protozoa can all cause gastrointestinal infections. The incidence of gastrointestinal infections is increasing, and active treatment should be sought.

　　Clinically, the diagnosis of elderly inflammatory bowel disease is mainly made through the following examination methods.

　　First, X-ray abdominal flat

　　For patients with severe active disease, X-ray abdominal film examination should be performed. In patients with toxic megacolon, signs such as mucosal edema (pressure痕), intestinal loop expansion, or intestinal perforation may be observed. In patients with small intestinal CD, intestinal obstruction or displacement of intestinal loops due to masses may be found.

　　Second, colonoscopy examination

　　This is one of the most important means for the diagnosis and differential diagnosis of the disease. It not only allows direct observation of mucosal lesions and their extent but also enables biopsy for obtaining a histological diagnosis. The lesions of UC often start from the rectum and extend upwards continuously and diffusely. The endoscopic features include:

　　1. The mucosa is diffusely congested and edematous, with blurred and disordered vascular patterns. The mucosa is rough, presenting as fine granules, is friable and prone to bleeding, and may have purulent and bloody secretions adhering to it;

　　2. At the obvious lesions, there may be diffuse multiple erosions or superficial ulcers of varying sizes and shapes, which may fuse;

　　3. Chronic lesions may show shallowening, blunting, or disappearance of the colon pouches, pseudopolyps, bridging mucosa, etc. Under colonoscopy, histological examination of the mucosal tissue during the active phase shows diffuse chronic and acute inflammatory cell infiltration, cryptitis, crypt abscesses, erosion, ulcers, and during the remission phase, changes such as glandular deformation, disordered arrangement, and decreased goblet cells, indicating mucosal atrophy.

　　The distribution of CD (Crohn's disease) is segmental, with oral thrush-like or longitudinal or creeping ulcers visible. The mucosa around the ulcers is normal or hyperplastic, presenting as pebble-like. The intestinal lumen is narrowed, the intestinal wall is rigid, and inflammatory polyps may be present. The mucosa between the affected intestinal segments appears normal. Deep biopsy at the lesion site can reveal non-caseating granulomas or lymphocyte aggregates in the lamina propria of the mucosa.

　　Three, X-ray造影 examination

　　Based on clinical manifestations, barium enema of the small intestine or barium enema examination can be performed, and combined when necessary. Its sensitivity is not as good as colonoscopy, and biopsy cannot be performed. It is generally not suitable to perform barium enema examination for severe or fulminant UC. The X-ray features of UC mainly include:

　　1. The mucosa is rough and (or) granular-like;

　　2. The intestinal margin presents as bristly or jagged, with multiple small pit shadows and filling defects visible in the intestinal wall;

　　3. The colon pouches disappear, the intestinal tract shortens, and may present as a lead pipe-like appearance.

　　The X-ray manifestation of CD shows multifocal, segmental intestinal inflammatory lesions, which include rough and紊乱ed mucosal folds, longitudinal fissure-like ulcers, pebble sign, stricture, fistula, and pseudopolyp formation, etc.

　　In general, elderly patients with inflammatory bowel disease (IBD) should adhere to the principles of soft, easy-to-digest, and high-nutrition food, with small and frequent meals and regular and quantitative meals. Specifically, there are the following aspects:

　　1, It is advisable to eat two-thirds of the normal meal size for each meal, and eat 4-5 times a day.

　　2, Reduce the intake of greasy and fried foods. If there are people with lactose intolerance, they should reduce the intake of milk and dairy products. Also, avoid foods that cause intestinal bloating such as soybeans and taros, and it is also advisable to eat less of the type of food that is easy to cause allergies, such as fish, shrimp, crabs, and silkworms.

　　3, Limit the intake of high-fiber foods such as nuts, corn, and some vegetables. High-fiber foods promote intestinal peristalsis, and if the small intestine is not fully digested, it may also lead to diarrhea. Therefore, it is generally recommended to adopt a low-fiber, low-residue diet.

　　4, Provide adequate calories and high-quality protein, inorganic salts, and vitamins. Avoid刺激性 food, such as chili, alcohol, and cold drinks.

　　5, IBD patients often lack folic acid, vitamins A, B6, D, K, and various nutrients such as calcium and iron. They should eat foods rich in these nutrients.

　　The treatment of elderly inflammatory bowel disease is similar to that of young people with inflammatory bowel disease. Corticosteroids and immunosuppressants are not contraindications for the elderly, but they should be used with caution and try to avoid adverse reactions. Attention should be paid to common accompanying diseases in the elderly, such as diabetes, heart disease, hypertension, osteoporosis, etc. The use of sulfonamides in the elderly can cause depression, and the use of corticosteroids is prone to cause fractures.
　　The frequency of systemic use of corticosteroids in elderly ulcerative colitis is higher, as Woolrich found that 58% of elderly patients with ulcerative colitis need to take prednisone orally, 30% need intravenous injection, while 29% of young people take prednisone orally and 11% need intravenous injection.
　　There are different opinions on the use of corticosteroids in the treatment of Crohn's disease. Harper believes that the amount of corticosteroids used in elderly Crohn's disease is less than that in young people with Crohn's disease. Some scholars believe that there is no significant difference between elderly and young people with Crohn's disease in the use of corticosteroids.