Have you had your appendix removed? Just had it done? It’s important to follow up within a year after surgery, as your risk of being diagnosed with Crohn’s disease is several times higher than the general population. How old were you when you had your appendix removed? Less than 20 years old? Congratulations, you’re less than half as likely to get ulcerative colitis as anyone else! The two main types of inflammatory bowel disease include Crohn’s disease and ulcerative colitis (ulcerative nodes for short). Crohn’s disease, formerly known as segmental enteritis, is a multiple transmural inflammatory disease that can involve any part of the GI tract; ulcerative colitis is a continuous, diffuse inflammation of the intestinal mucosa and submucosa that spreads upward from the rectum. Although inflammatory bowel disease is a benign disease, it is extremely harmful to people because it has a significant impact on intestinal function, cannot be cured (mainly referring to Crohn’s disease), and may have recurrent intestinal bleeding, intestinal perforation, intestinal obstruction, and other complications. The exact etiology of inflammatory bowel disease is not known, and its occurrence is currently thought to be related to a combination of genetic and environmental factors (acquired). Appendicitis and appendectomy are also considered to be among the acquired factors influencing the development of inflammatory bowel disease. Simply put, the probability of being diagnosed with Crohn’s disease increases after appendectomy, but the probability of developing ulcerated nodes may decrease. Appendectomy and Crohn’s disease Kaplan GG et al. analyzed 710,000 patients who underwent appendectomy for various reasons (Gut 2007;56:1387-1392), and more than 1600 patients were diagnosed with Crohn’s disease during a mean follow-up period of 15.6 years, a rate approximately 1.52 times higher than that of the general population during the same period. Further analysis, as seen in Figure 1, shows that the closer to the time of appendectomy, the more likely the diagnosis of Crohn’s disease. The probability of a diagnosis of Crohn’s disease within six months after appendectomy was 8.69 times higher than in the general population (referred to as the norm), and this value was 3.16 times higher between six months and one year after surgery, decreasing gradually thereafter, but higher than in the norm over a 10-year period. This author later further confirmed by a meta-analysis that the probability of diagnosing Crohn’s disease within one year after surgery was 6.69 times higher than in the general population, decreasing year by year thereafter (Am J Gastroenterol 2008;103:2925-31. as shown in Figure 2). We can also see from Figure 1 that those patients who had an appendectomy but whose postoperative diagnosis was not appendicitis had a more pronounced increase in the probability of postoperative diagnosis of Crohn’s disease, and this increase took almost 20 years to decrease to normative levels. The increased incidence of Crohn’s disease after appendectomy is generally considered to be due to “diagnostic bias”, which is, frankly, misdiagnosis or incomplete diagnosis. First, the early symptoms of Crohn’s disease and appendicitis are very similar, both presenting with right lower abdominal pain, and both diseases can present with leukocytosis in the blood, making them easily confused; and the interval between the earliest symptoms of Crohn’s disease and the diagnosis is often 2-3 years, during which the disease may be misdiagnosed as appendicitis. In addition, Crohn’s disease itself can also involve the appendix and cause inflammation. It has been found that inflammation of the appendix can be found in 40% of patients with Crohn’s disease who have their appendix removed for other complications (Vichow Arch 2002;440:397-403), and these patients may be diagnosed with appendicitis alone and undergo appendectomy. Therefore, for those patients with a high suspicion of appendicitis but Crohn’s disease cannot be excluded, such as those with a family history of Crohn’s disease, combined with long-term chronic abdominal pain and diarrhea or low fever, anemia or hypoproteinemia found on preoperative examination, and abscess enterocutaneous fistula formation found intraoperatively or postoperatively, careful intraoperative exploration and close postoperative follow-up should be performed, and if necessary, endoscopy should be performed during follow-up in order to detect and treat Crohn’s disease in a timely manner. So, is it possible to rule out Crohn’s disease in patients with a diagnosis of appendicitis with more intensive testing before surgery? Some typical patients and experienced physicians may be able to accomplish this task, but for most patients there are two difficulties: one is a technical limitation, as the diagnosis of Crohn’s disease is highly dependent on colonoscopy, and most patients with appendicitis are emergency patients who do not have time to complete bowel preparation and colonoscopy; the other is an economic consideration, as the annual incidence of appendicitis is about 1/1000, while the annual incidence of inflammatory bowel disease is between 1 and 2. The annual incidence of inflammatory bowel disease in China is about 1 to 2/100,000, and even if the incidence increases 10-fold in the first year after appendicitis, it is only 1 to 2/1,000, so it may not be economical to perform extensive screening for this uncommon condition. Therefore, careful intraoperative exploration and close postoperative follow-up of high-risk patients are more feasible. I once admitted a patient with a postoperative intestinal fistula after appendicitis, a young male in his 20s, who had the procedure done at an outside hospital. At that time, I despised the surgeon of the outside hospital: I had to cut the appendix and created an intestinal fistula, the surgical technique was so bad! Later, the patient underwent an ileocecal resection in our hospital, and the post-operative pathology revealed Crohn’s disease! It dawned on me that such an “appendicitis” is likely to result in an intestinal fistula for anyone who cuts it. From then on I had an intuitive understanding of the association between appendicitis and Crohn’s disease. Appendicitis and ulceration Frisch M et al. analyzed 710,000 patients who underwent appendectomy for various reasons, and over 1,100 patients were diagnosed with ulceration during an average follow-up period of 15.6 years, which is approximately 0.80 to 0.88 times the rate of the general population over the same period. (Wait a minute, why is this statement so similar to the previous Kaplan GG study? Because they used two of the same databases: the Swiss and Danish National Health Service databases. Many Western countries have such national health databases, which hold a wealth of detailed information on medical records. These databases allow easy access to large samples of epidemiological information, which can provide reliable information for medical research and the formulation of medical policies and regulations. At present, regional databases are also being established for certain diseases in China, but a national multi-disease database has not yet started due to various conditions). Further analysis revealed that the decreased probability of developing ulcerative nodes after appendectomy was strongly related to the age at the time of appendectomy, as shown in Figure 3. The incidence of ulcerative nodes in patients who had their appendix removed before the age of 20 was only equivalent to 30%-40% of the norm, while the incidence of ulcerative nodes in patients who had their appendix removed after the age of 20 was not significantly different from that of the norm. Since appendicitis has a certain rate of misdiagnosis, not all patients who undergo appendectomy are appendicitis patients (for example, Crohn’s disease as mentioned earlier may also be diagnosed as appendicitis). Interestingly, if patients with appendicitis are counted separately from those with non-appendicitis, there is a reduction in the incidence of ulcerative nodes only in those patients who do have appendicitis (Figure 4), and this difference is also very significant. Therefore, it is not appendectomy that really reduces the incidence of ulcerative nodes, but appendicitis itself! This conclusion is largely accepted by the medical community Why would appendicitis in adolescence reduce the incidence of ulcerative nodes? In four words: it is not clear. The more current concern is that appendicitis and appendectomy reduce a chemokine called CCL2, which affects the migration and activation of immune cells Th17 cells associated with colonic inflammation The figure below is a schematic diagram from the article, it does not matter if you can’t read it, you can bluff it. To summarize this time: appendicitis and appendectomy itself is not the cause of Crohn’s disease, but Crohn’s disease is easily treated as appendicitis with appendectomy, so the possibility of being diagnosed with Crohn’s disease increases within a certain period after appendectomy. Appendicitis and appendectomy may indeed reduce the incidence of ulcerative nodes, but two conditions must be met: first, the appendix must be removed before age 20, and second, it needs to be determined that the appendix was removed for appendicitis. If you don’t have time to read the previous paragraphs, reading this one will be enough.