Studies specifically on the long-term outcomes of cecal ulcers in asymptomatic patients are scarce. Our study demonstrated that clinically significant diseases, including colonic tuberculosis, ulcerative colitis and Crohn’s disease could develop in a portion of patients with asymptomatic cecal ulcers. The endoscopic features that predict a clinically significant disease include ulcers larger than 1 cm, terminal ileum involvement and ulcers with irregular fold.
Previous reports have focused on symptomatic (such as fever or lower gastrointestinal bleeding) patients with cecal ulcers [1, 8,9,10]. One case series from India reported 58 symptomatic patients who had cecal ulcers with or without ileum involvement . The most common etiology was non-specific ulcers or infectious nature. There were no endoscopic features that clearly identified ulcers with a specific cause.
The differential diagnosis of cecal ulcer depends largely on the nature of the patient population. Without symptoms of acute illness, such as fever and abdominal pain, the causes may be narrowed down to chronic inflammatory diseases. In our cohort, none of the patients reported gastrointestinal symptoms. Moreover, all 24 patients had a normal white blood cell count and hemoglobin level. Only one patient with colonic tuberculosis had an elevated C-reactive protein level (4.47 mg/dL). Guaiac-based fecal occult blood test was trace positive in only one patient and negative in the rest. This observation was consistent with a previous report by Rodriguez-Lago et al. showing that 23% of patients had a negative fecal immunochemical test 2 years before inflammatory bowel disease was diagnosed . Early detection of preclinical disease may be the reason that the cases in our study had normal laboratory data. In such cases, the endoscopic features of asymptomatic patients with a significant disease may not be as typical as those of their symptomatic counterparts. For example, one report of 69 patients with intestinal tuberculosis showed that up to 32.8% presented with ileocecal valve deformities and as high as 44.8% patients presented with luminal stenosis, either in the terminal ileum or other parts of the intestine . In our two cases, the endoscope could pass through the ileocecal valve without resistance and other specific findings of intestinal tuberculosis, such as patulous ileocecal valve, were not observed [12, 13].
The diagnosis of intestinal tuberculosis is typically made by the evidence of a typical histological picture. For example, granuloma could be found in up to 73% of patients with a diagnosis of intestinal tuberculosis (50 out of 68 patients) . In our cases, the first patient had typical histological findings in the initial endoscopic exam, including granulomatous inflammation and positive acid-fast stain bacilli. In the second case, however, the diagnosis was obscure. The endoscopic biopsies were performed 3 times and results were all inconclusive. Tuberculosis cultures of endoscopic samples were also negative. The diagnosis was made based on positive quantiFERON test and complete remission after antituberculosis medications.
Atypical presentation was also reported in the early course of ulcerative colitis. A previous study reported that up to 19.2% (46 out of 240 cases) of ulcerative colitis cases had an atypical distribution, such as appendiceal orifice inflammation in the initial endoscopic exam . The case of ulcerative colitis in our study had only peri-appendiceal and terminal ileum ulcers initially. The diagnosis was not made until 3 years later when bloody stool occurred and the presence of a typical endoscopic picture of proctitis was observed.
Several endoscopic features have been reported to differentiate Crohn’s disease from intestinal tuberculosis, such as longitudinal ulcers, and cobblestone appearance [13, 15]. The case with Crohn’s disease in our study did not show these two typical endoscopic characteristics and the location of the involved area was confined to the cecal and terminal ileum. It may again represent a case in which an early natural course was discovered due to the initial screening colonoscopy.
There are a few limitations in this study. First, the case numbers were relatively low. However, the prevalence of both asymptomatic inflammatory bowel disease and intestinal tuberculosis in our cohort was in line with previous studies. The prevalence of asymptomatic inflammatory bowel disease was 0.056–0.355% in Western countries and 0.06% in Japan in individuals participating in colon cancer screening [4, 11, 16,17,18]. In our cohort, the prevalence of inflammatory bowel disease was 0.059% (2 cases out of 34,036 persons), which is very similar to the rate seen in Japan. Since we focused on cecal ulcers only, the number of patients with ulcerative colitis could be underestimated. Besides inflammatory bowel disease, intestinal tuberculosis was diagnosed in 2 cases out of 34,036 asymptomatic persons in our study. This prevalence was also close to the prevalence in Japan (5 cases in 236,000 persons) . Second, 8 patients refused to have a follow-up colonoscopy in the out-patient department. The main reason for refusal was that the patients felt well and did not have any relevant symptoms. Without follow-up, we could not determine their subsequent outcome. Nonetheless, a previous report showed that 36% of patients with a diagnosis of asymptomatic inflammatory bowel disease developed symptoms in an average of 25 months . The clinical follow-up duration of these 8 patients was 49.1 months (range 19–99 months) in the out-patient department. Without further development of symptoms, we speculate that the lack of follow-up data for these patients may have little clinical significance. Third, the prevalence of both intestinal tuberculosis and inflammatory bowel disease differs among regions, and therefore the results of this study might not be representative of other countries.