Clinical Analysis and Identification of Pediatric Patients with Colonic Ulceration

Clinical Analysis and Identification of Pediatric Patients with Colonic Ulceration | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Clinical Analysis and Identification of Pediatric Patients with Colonic Ulceration Yaying You, Yijing Tao, Yanwen Xu, Yi Cao, Haixia Feng, Qingqing Wu, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4603636/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 01 Nov, 2024 Read the published version in BMC Pediatrics → Version 1 posted 10 You are reading this latest preprint version Abstract Background A wide variety of diseases mimic inflammatory bowel disease (IBD). This study aimed to reduce the misdiagnosis among children with colonic ulcers, unfolding the pediatric disease profiles. Methods Eighty-six pediatric patients with colonic ulcers detected by colonoscopy were enrolled in the retrospective study. Children were divided into different groups according to the final diagnosis. The clinical characteristics, laboratory examinations and histopathological results were compared between the groups. Results IBD (n = 37) was just responsible for 43% of patients with colonic ulceration. Other diagnosis mainly included autoimmune diseases (n = 9), infectious enteritis (n = 13), gastrointestinal allergy (n = 8), and other diseases (n = 19). Comparing IBD and non-IBD groups, children with IBD had a higher frequency of symptoms like weight loss/failure to thrive ( P < 0.001), perianal lesions ( P = 0.001), and oral ulcers ( P = 0.022), and higher expression levels of platelet ( P = 0.006), neutrophil-to-lymphocyte ( P = 0.001), erythrocyte sedimentation rate ( P < 0.001), C-reactive protein ( P < 0.001), Immunoglobulin G ( P = 0.012), Interleukin-1β ( P = 0.003), IL-6 ( P = 0.024) and TNF-α ( P = 0.026). Otherwise, expression levels of hemoglobin ( P < 0.001) and albumin ( P = 0.001) were lower in IBD patients. Besides, a wider ulcer range distribution in the lower gastrointestinal tract was found in the IBD group ( P < 0.001). Conclusions We displayed potential indicators (like platelet, neutrophil-to-lymphocyte ratio and ulcer distribution character) to help diagnose pediatric IBD with colonic ulcers differentiating from other disorders more prudent. Colonoscopy Ulcer Colon Diagnosis Inflammatory bowel disease Figures Figure 1 Figure 2 What is known: Many diseases can mimic IBD and reducing the misdiagnosis of IBD children is essential for the treatment and prognosis. Inflammatory factors like erythrocyte sedimentation rate, and fecal calprotectin have clinical value in diagnosing IBD. What is new: In our study, we investigated that IBD was just responsible for 43% of patients with colonic ulceration. Some potential indicators (like platelet, neutrophil-to-lymphocyte ratio and ulcer distribution character) may contribute to the diagnosis of pediatric IBD with colonic ulcers. Introduction Colonic ulcerations are a kind of localized defect of mucosal surface tissue found in colon and rectum[1]. The etiology of colonic ulceration is multiple, including inflammatory bowel disease (IBD), infectious colitis, allergic colitis, et al.[2-5]. Therefore, a differential diagnosis is required for further treatment and prognosis evaluation[6]. It is challenging, and misdiagnosis is not rare in clinical practice. Many diseases (including infection, drug-induced disease, vascular disorders, diverticular disease, diversion proctocolitis, and immune disorders) can mimic IBD in clinical and pathological features[7]. Inflammatory factors like erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and fecal calprotectin (FCP) have been found to have potential clinical diagnosis value with IBD but still need higher specificity[8,9]. In most cases, acute infectious colitis is easily identified by clinical symptoms with no requirement for colonoscopy. But the patients with negative findings in pathogen tests, who present gastrointestinal bleeding, respond poorly to treatment or have previous chronic gastrointestinal disorders, may undergo colonoscopic examination and confront the complex differential diagnosis[10]. Gastrointestinal-involved vasculitis, such as immunoglobulin A vasculitis and systemic lupus erythematosus (SLE), could be very similar to IBD in the symptoms, endoscopic findings, and histological assessment. European Crohn's and Colitis Organisation (ECCO) recommended some features to help in the differential diagnosis between primary vasculitis and IBD[7]. The imaging, serological, fecal, and molecular tests could assist differentiation. The manifestation of IBD in the pediatric population is more complicated and less specific than in adults for a higher ratio of genetic factors involved. It is well-known that IBD is diagnosed based on an exclusive method. Therefore, it is prone to be overdiagnosed in patients with colonic ulceration[1,2,11]. Pediatricians should also pay attention to gastrointestinal allergic diseases, which are more prevalent in children and increasing[12]. The data focused on the pediatric population is limited. To avoid diagnostic pitfalls, we observed the colonoscopy findings of ulcer features and combined them with the clinical manifestations and biochemical indexes of patients for the further recognition of related diseases, especially between IBD and non-IBD diseases. We summarized the differential manifestations of patients in the study and hoped to provide an alert for the misdiagnosis of children with colonic ulceration. Materials And Methods 2.1 Patients and Study Design From December 2014 to June 2022, 86 pediatric patients (age from 1 month to 15 years, and male: female = 42: 44) were analyzed in the study from Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine. Inpatients with colonic ulceration discovered by colonoscopy for the first time were eligible for the inclusion criteria. The patients with ulcers that are isolated in rectum were excluded. All children had relatively complete medical history records. Demographic parameters, clinical characteristics, and laboratory examinations were collected from the medical record retrieval system. Demographic parameters included age and gender. Clinical characteristics harbored weight loss/failure to thrive, abdominal pain, diarrhea, constipation, hematochezia, fever, perianal lesions, rash, oral ulcer, and joint pain. The colonoscopy findings were analyzed retrospectively in combination with histopathological results. Furthermore, we divided the lower gastrointestinal tract into terminal ileum, ileocecal part, ascending colon, transverse colon, descending colon, sigmoid colon and rectum; every part with ulceration meant one score, and then we accumulated total score. The etiology was determined by clinical manifestation, examination, and long-term follow-up. The IBD was diagnosed after excluding infectious, allergic, immunologic and other diseases. When genetic mutation associated with the primary immune deficiencies was detected, we diagnosed those patients as monogenic IBD-like disorders but not ulcerative colitis (UC) or Crohn's disease (CD) in this study[7]. Nonspecific colonic ulcer was diagnosed in the patients who ruled out other diseases and recovered well without any treatment during the follow-up. 2.2 Statistical analysis All data were analyzed using SPSS 26.0 (SPSS, Inc., IBM, Chicago, Illinois, USA). The measurement data were expressed using a median with an interquartile range (IQR). The enumeration data were presented by frequency or proportions. Mann–Whitney non-parametric test, Pearson’s chi-squared test or Fisher’s exact test were used for the comparison between different groups. A P value < 0.05 was defined as the statistical significance. 2.3 Ethics approval In accordance with the Declaration of Helsinki, the study was approved by the Ethics Committee of Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (XHEC-D-2022-250). Results 3.1 The diagnosis of children finding colonic ulcer Eighty-six pediatric patients finding colonic ulcers were enrolled in the research. Etiological analysis of patients was shown in Table 1. Of note, the most common diagnosis was IBD (37/86), including UC (8/86, 9.3%), CD (22/86, 25.6%), and Monogenic IBD-like disorders (7/86, 8.1%) with the mutation of IL10RA , EP300 mutation, PIK3CD mutation, Wiskott-Aldrich Syndrome, and immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome, respectively. Otherwise, there were autoimmune diseases (6 cases of IgA vasculitis (7.0%), 2 cases of other vasculitis (2.3%), and 1 case of SLE (1.2%), respectively), and gastrointestinal allergy (2 cases of food protein-induced enterocolitis (FPIES) (2.3%), 3 cases of eosinophilic gastroenteritis (3.5%), and 3 cases of other gastrointestinal allergy diseases (3.5%), respectively). A high ratio of children was also diagnosed with infectious enteritis (13/86, 15.1%). Other causes of colonic ulcers included nonspecific colonic ulcers (14/86, 16.3%), neonatal necrotizing enterocolitis (NEC) (1, 1.2%), Hirschsprung’s disease (1, 1.2%), Langerhans cell histiocytosis (LCH) (1, 1.2%), Digestive perianastomotic ulcerations (1, 1.2%), and anal fistula (1, 1.2%). Table 1 Etiological analysis of patients with colonic ulceration. Etiology Number (n = 86) n (%) IBD (n= 37) *UC 8 (9.3%) *CD 22 (25.6%) Monogenic IBD-like disorders 7 (8.1%) Non-IBD (n= 49) Autoimmune diseases Vasculitis IgA vasculitis (Henoch-Schönlein purpura) 6 (7.0%) Other vasculitis 2 (2.3%) SLE 1 (1.2%) Infectious enteritis 13 (15.1%) Gastrointestinal allergy FPIES 2 (2.3%) Eosinophilic gastroenteritis 3 (3.5%) Other gastrointestinal allergy 3 (3.5%) Others Nonspecific colonic ulcer 14 (16.3%) NEC 1 (1.2%) Hirschsprung’s disease 1 (1.2%) LCH 1 (1.2%) Digestive perianastomotic ulcerations 1 (1.2%) Anal Fistula 1 (1.2%) IBD = Inflammatory bowel disease, *UC = Ulcerative colitis with no monogenic abnormality, *CD = Crohn's disease with no monogenic abnormality, SLE = Systemic lupus erythematosus, FPIES = Food protein-induced enterocolitis, NEC = Neonatal necrotizing enterocolitis, LCH = Langerhans cell histiocytosis 3.2 Comparison of clinical characteristics in patients with colonic ulceration Children were divided into IBD (n = 37) and non-IBD (n = 49) groups for further exploring the potential specific indicators of IBD. Statistical analysis displayed no significant difference between IBD and non-IBD groups in age and gender. The frequency of weight loss/failure to thrive ( P < 0.001), perianal lesions ( P =0.001), and oral ulcer ( P = 0.022) was significantly higher in IBD group than in non-IBD group (Table 2). The frequency of fever is higher in IBD group (18, 48.6%) than in non-IBD group (14, 28.6%), even though there was no significant difference between two groups ( P = 0.057). Then, we further divided children into Normal IBD (UC or CD with no monogenic abnormality)， Monogenic IBD-like disorders and non-IBD groups (Table S1 – S3). Statistical analysis showed that the age of children with monogenic IBD-like disorders is significantly younger than children in Normal IBD or non-IBD groups ( P < 0.001). Table 2 Comparison of characteristics of IBD and non-IBD patients. Events IBD (n = 37), n (%) Non-IBD (n = 49), n (%) P value Age, y, 0.115 age < 2 y 8 (21.6%) 11 (22.4%) 2 y ≤ age < 6 y 3 (8.1%) 9 (18.4%) 6 y ≤ age < 10 y 8 (21.6%) 16 (32.7%) Age ≥ 10 y 18 (48.6%) 13 (26.5%) Gender (Male/Female) 16/21 (43.2%/56.8%) 26/23 (53.1%/46.9%) 0.367 Abnormal findings Weight loss/failure to thrive 16 (43.2%) 6 (12.2%) <0.001*** Abdominal pain 17 (45.9%) 33 (67.3%) 0.046* Diarrhea 19 (51.4%) 20 (40.8%) 0.331 Constipation 4 (10.8%) 6 (12.2%) 1.000 Hematochezia 15 (40.5%) 25 (51.0%) 0.335 Fever 18 (48.6%) 14 (28.6%) 0.057 Perianal lesions 13 (35.1%) 3 (6.1%) 0.001** Rash 7 (18.9%) 8(16.3%) 0.754 Oral ulcer 7 (18.9%) 1 (2.0%) 0.022* Joint pain 4 (10.8%) 2 (4.1%) 0.432 IBD = Inflammatory bowel disease. * P <0.05, ** P <0.01, *** P <0.001 3.3 Comparison of biochemical indexes in patients with colonic ulceration The biochemical indexes were then analyzed in different groups (Table 3, Table S4 – S6). The levels of hemoglobin ( P < 0.001) and albumin ( P = 0.001) were lower in IBD group than in non-IBD group, While the levels of platelet ( P = 0.006), neutrophil-to-lymphocyte ratio (NLR) ( P < 0.001), ESR ( P < 0.001), CRP ( P < 0.001), Immunoglobulin G (IgG) ( P = 0.012), and Interleukin-1β (IL-1β) ( P = 0.003), IL-6 ( P = 0.024) and TNF-α ( P = 0.026) were significantly higher in IBD group than in non-IBD group. In addition, the level of FCP was > 1500 ug/g in 22 cases (78.6%) of IBD children and in 14 cases (58.3%) of non-IBD children ( P = 0.065) (Table 3). NLR, ESR, CRP and TNF-α showed higher level in CD group than in gastrointestinal allergy group (Table S6). Table 3 Comparison of biochemical indexes of IBD and non-IBD patients. Events IBD (n = 37) Non-IBD (n = 49) P value Hemoglobin, g/dL, n, median (IQR) 37, 109.00 (87.50 - 121.00) 49, 127.00 (111.50 - 132.50) <0.001*** Albumin, mg/dL n, median (IQR) 37, 36.60 (31.45 - 41.25) 49, 42.60 (37.20 - 45.55) 0.001** Platelet, 10^9/L n, median (IQR) 37, 397 (310 - 521) 49, 302 (258 - 391) 0.006** D-Dimer n, median (IQR) 29, 0.55 (0.32 - 0.86) 42, 0.315 (0.23 – 0.827) 0.124 NLR n, median (IQR) 37, 2.49 (1.80 - 4.42) 49, 1.41 (0.96 - 2.70) 0.001** AST, U/L n, median (IQR) 37, 29.00 (19.85 - 40.50) 49, 34.00 (25.35 - 42.15) 0.081 ALT, U/L n, median (IQR) 37, 16.00 (10.00 - 21.00) 49, 19.00 (11.00 - 26.00) 0.230 ESR, mm/h, n, median (IQR) 36, 36.50 (20.50 – 64.25) 33, 16.00 (2.50 – 26.00) <0.001*** CRP, mg/L <0.001*** <8, n (%) 10 (27.0%) 33 (67.3%) ≥8, n (%) 27 (73.0%) 16 (32.7%) Positive fecal transferrin, n (%) 16 (84.2%) 27 (90.0%) 0.877 Positive fecal occult blood, n (%) 21 (60.0%) 28 (62.2%) 0.840 FCP, ug/g 0.065 ≤ 50, n (%) 1 (3.6%) 2 (8.3%) 50 < FCP ≤ 500, n (%) 1 (3.6%) 6 (25%) 500 < FCP ≤ 1000, n (%) 2 (7.1%) 2 (8.3%) 1000 1500, n (%) 22 (78.6%) 14 (58.3%) IgA, g/L 0.279 < 0.7, n (%) 5 (17.9%) 7 (26.9%) 0.7 ≤ IgA < 4, n (%) 20 (71.4%) 18 (69.2%) ≥ 4, n (%) 3 (10.7%) 1 (3.8%) IgG, g/L 0.012* < 7, n (%) 2 (7.1%) 7 (26.9%) 7 ≤ IgG < 16, n (%) 20 (71.4%) 18 (69.2%) ≥ 16, n (%) 6 (21.4%) 1 (3.8%) IL-8, pg/mL 0.921 < 62, n (%) 10 (43.5%) 9 (45.0%) ≥ 62, n (%) 13 (56.5%) 11 (55.0%) IL-1β, pg/mL 0.003** < 5, n (%) 2 (8.7%) 10 (50.0%) ≥ 5, n (%) 21 (91.3%) 10 (50.0% IL-6, pg/mL 0.024* < 5.9, n (%) 4 (17.4%) 10 (50.0%) ≥ 5.9, n (%) 19 (82.6%) 10 (50.0%) IL-10, pg/mL 0.988 < 9.1, n (%) 15 (65.2%) 13 (65.0%) ≥ 9.1, n (%) 8 (34.8%) 7 (35.0%) TNF-α, pg/mL 0.026* < 8.1, n (%) 0 (0.0%) 4 (20.0%) ≥ 8.1, n (%) 23 (100.0%) 16 (80.0%) IL-2R, pg/mL 0.080 50, n (%) 4 (20.0%) 5 (45.5%) IBD = Inflammatory bowel disease, NLR = neutrophil-to-lymphocyte ratio, AST = Alanine aminotransferase, ALT = Alanine aminotransferase, ESR = Erythrocyte sedimentation rate, CRP = C-reactive protein, FCP = Fecal calprotectin, IgA = Immunoglobulin A, IgG = Immunoglobulin G, IL-8 = Interleukin-8, IL-1β = Interleukin-1β, IL-6 = Interleukin-6, IL-10 = Interleukin-10, TNF-α = tumor necrosis factor-α, IL-2R = Interleukin-2 receptor, 25-(OH)-VitD = 25-hydroxyvitamin D. * P <0.05, ** P <0.01, *** P <0.001 3.4 The comparison of endoscopic characteristics in patients with colonic ulceration Next, we collected the endoscopic figures of patients with different diagnosis (UC, CD, monogenic IBD-like disorders and non-IBD, respectively) in Figure 1. We sorted out the endoscopic information of patients (Table 4, Table S7 - S8). The existence of upper gastrointestinal ulceration presented no significant difference in IBD and non-IBD groups. Colonoscopy revealed that ulcers could be found in any segment of the colon, and a wider ulcer distribution range in lower gastrointestinal tract was found in IBD group than in non-IBD group ( P < 0.001), especially between CD and infectious enteritis groups. Besides, Table 4 displayed that cobblestone appearance mainly showed in IBD group ( P = 0.031). Table 4 Comparison of endoscopic characteristics in IBD and non-IBD patients. Events IBD (n = 37) Non-IBD (n = 49) P value Ulcer distribution Upper gastrointestinal ulceration, n (%) 9 (24.3%) 4(10.3%) 0.104 *Score of ulceration in lower GI, median (IQR) 5 (2 – 6) 2 (1 – 2) <0.001*** Abnormal findings Erythema, n (%) 1 (2.7%) 3 (6.1%) 0.631 Cobblestone appearance, n (%) 4 (10.8%) 0 (0.0%) 0.031* Narrow, n (%) 3 (8.1%) 2 (4.1%) 0.648 Distortion of ileocecal valve, n (%) 3 (8.1%) 0 (0.0%) 0.076 IBD = Inflammatory bowel disease, * Score of ulceration in lower GI: We divided the lower gastrointestinal (GI) tract into terminal ileum, ileocecal part, ascending colon, transverse colon, descending colon, sigmoid colon and rectum; every part with ulceration meant one score and we accumulated total score. * P <0.05, *** P <0.001 3.5 The comparison of histopathological results in patients with colonic ulceration The histopathological presentations were including inflammatory cell infiltration, cryptitis, crypt abscess, granulation tissues hyperplasia, and granuloma (Figure 2). We found IBD patients presented more pathological changes, including crypt abscess ( P = 0.013), granulation tissues hyperplasia ( P < 0.001), and granuloma ( P = 0.016), compared to non-IBD patients (Table 5). When comparing Normal IBD, Monogenic IBD-like disorders and non-IBD groups (Table S9), only the characteristic of granulation tissues hyperplasia had statistical differences between children with monogenic IBD-like disorders (3, 42.9%) and non-IBD groups (1, 2.1%). Table 5 Comparison of histopathological results in IBD and non-IBD patients Events IBD (n = 37) Non-IBD (n = 48) P value Cryptitis, n (%) 26 (70.3%) 31 (64.6%) 0.580 Crypt abscess , n (%) 13 (35.1%) 6 (12.5%) 0.013* Granulation tissues hyperplasia , n (%) 13 (35.1%) 1 (2.1%) <0.001*** Granuloma , n (%) 9 (24.3%) 2 (4.2%) 0.016* IBD = Inflammatory bowel disease. * P <0.05, *** P <0.001 Discussion With the development of endoscopic technology, colonic ulcers were found in children with different diagnosis. Due to the particular stage of growth and development in children and different disease spectrum from adults, it is essential to do early differential diagnosis and provide precise treatment. Our study displayed some potential unique indicators for the help of the diagnosis of pediatric IBD differentiating from other disorders with colonic ulcers, though we need larger sample size to confirm the findings. In the total of 86 pediatric patients found with ulcers by colonoscopy, the most common diagnosis was IBD. Early-onset IBD patients (<10 years), especially very early-onset IBD (VEO-IBD) patients (<6 years), present a closer relationship with genetic mutations[13]. We defined VEO-IBD patients as monogenic IBD-like disorders when they have a monogenic mutation according to ECCO[7]. In our study, 3 cases were with the mutation of IL10RA , which was of high frequency in monogenic IBD-like disorders, and the conventional therapy of IBD may have poor efficacy, even with haematopoietic stem cell transplantation [14,15]. Four cases were also with genetic abnormality, including EP300 mutation, PIK3CD mutation, Wiskott-Aldrich Syndrome, and IPEX syndrome, respectively. These children need early gene detection to confirm the diagnosis for the severe disease progression[16]. Autoimmune diseases had 9 cases, mainly including IgA vasculitis (6/86). IgA vasculitis is one of the most frequent vasculitides in childhood and had similar gastrointestinal manifestations (abdominal pain, hematochezia) with IBD, which needs care for the prognosis [17]. A total of 8 cases of gastrointestinal allergy were found in our study, and the disease occurs frequently in children. Nambu et al. also found the most common diagnoses except for IBD in children who performed colonoscopies, were eosinophilic gastrointestinal disorders, which need food avoidance[18]. Our findings showed that the levels of NLR, ESR, CRP and TNF-α may distinguish IBD and gastrointestinal allergy. Furthermore, a high proportion of children had intestinal ulcers for infectious enteritis (13/86), which may alert us to strictly control the indications of colonoscopy examination. We mainly focused on comparing IBD with other diseases and the differences may help to increase the differential diagnosis of disease profile. The results displayed that the age of Normal IBD group was mainly ≥ 10 years (60.0%), while the age of children with monogenic IBD-like disorders was mainly < 2 years (85.7%), which was consistent with previous research [19]. Clinical symptoms of children with colonic ulcers, weight loss/failure to thrive, perianal lesions, and oral ulcers had a higher frequency in IBD children than in non-IBD children. These abnormal findings fulfilled the criteria of clinical features in IBD [20,21]. While the age of children was less than 6 years old, clinical characteristics and biochemical indexes lacked significant differences in different diseases. Our findings showed less abdominal pain found in IBD children. The cause indicates that the mild pain was easily neglected due to other serious complaints in this retrospective study. And abdominal pain is a subjective feeling while children may lack correct expression. Laboratory examinations presented lower hemoglobin and albumin expression levels in the IBD group than in the non-IBD group. These were typically elevated in active disease while mild IBD could show normal results in routine blood tests [21]. Sabery et al. found anemia as a predictor for IBD was 83% sensitivity, and albumin is also a sensitive maker when combined with inflammatory indexes like CRP or ESR [8,9]. The Intestinal ulcer lesions may contribute to the condition that IBD children are more susceptible to anemia than other diseases. Platelet aggregation at the colonic mucosae was common in colitis and IBD[22], and our findings of the level of platelet and D-Dimer is higher in IBD children, indicating the IBD children had an increased risk for thrombus development than children with other colitis. As a marker of reflecting systemic inflammation, NLR has been found to be significantly increased at diagnosis and active disease of IBD children compared with healthy subjects[23-25]. Our results further found that NLR was also considerably higher in IBD group than in non-IBD group, even though all patients had colonic ulceration. The expression levels of ESR and CRP were still significantly higher in IBD group. These markers may also be relatively sensitive and specific to distinguish IBD from other diseases in children with ulcers in colon. Besides, FCP is a kind of protein from neutrophils, considered as a noninvasive and valuable marker of intestinal inflammation[26,27]. We found that the expression levels of FCP between two groups did not show statistical differences ( P = 0.065). FCP in both IBD (78.6%) and non-IBD patients (58.3%) was mainly > 1500 ug/g. The reason indicates that young children have a higher baseline value of FCP compared with normal adults[27]. In addition, the research object in our study were all children with colonic ulceration, whose intestinal inflammation was relatively severe. Herein, FCP may not be sensitive to distinguishing IBD among children with colonic ulcerations. Otherwise, IgG was also at higher levels in IBD group. IBD is a disorder closely related to immune reaction. IgG was predicted to be associated with IBD severity and response to gut microbiota [28]. Pro-inflammatory factors including IL-1β, and TNF-α, were increasing the expression level in IBD group. The finding indicates that IL-1β may be a potential specific marker of IBD in pediatric patients. The upstream mechanisms and signal pathways of IL-1β may be interesting perspectives of pathogeny which identify IBD from colonic ulcerative diseases, like mediating NLRP3 activation which regulates the generation and maturation of IL-1β [29-31]. In addition, anti-TNF-α drugs have been widely used in treating children with IBD[32]. Anti- IL-1β may also be an effective therapeutic target in IBD patients in the future. Colonoscopy revealed statistical differences in ulcer distribution between IBD and non-IBD groups. The discrepancy in ulcer distribution range may help to distinguish colonic ulceration, especially between CD and infectious enteritis. Otherwise, cobblestone appearance was only found in IBD group, which fulfilled the criteria of endoscopic characteristics in CD[20]. Histopathological results play essential roles in the different diagnoses of intestinal disorders [21]. The characteristics of mucosal tissue with hematoxylin & eosin staining included cryptitis, crypt abscess, granulation tissues hyperplasia, granuloma, lymphocyte proliferation, and eosinophil infiltration. The histological phenotype is hardly distinguished for the overlapping in morphological aspects between IBD and non-IBD patients[10]. In children with colonic ulcers, we found the significant differences in the change of crypt abscess, granulation tissues hyperplasia, and granuloma between IBD and non-IBD groups. Granuloma is a kind of local change of chronic inflammation, which could be observed typically in CD [21]. Characteristic pathological changes still need further exploration in other intestinal disorders. Conclusion In conclusion, the etiologies caused by colonic ulcers are complex and diverse, and primary diseases are IBD, infectious enteritis, autoimmune diseases, and gastrointestinal allergy. Hemoglobin, albumin, platelet, NLR, ESR, CRP, IgG, IL-1β, IL-6, and TNF-α could be considered as essential reference indicators for IBD in children with colonic ulcers. The sensitivity and specificity still need a large sample size to verify these indexes. The different changes found in colonoscopy in the study are hoped to help further understand intestinal diseases and improve the diagnosis in children with colonic ulcers. Abbreviations CD: Crohn's disease CRP: C-reactive proteinA ECCO: European Crohn's and Colitis Organisation ESR: erythrocyte sedimentation rate FCP: fecal calprotectin FPIES: food protein-induced enterocolitis IBD: Inflammatory bowel disease IgG: Immunoglobulin G IL-1β: Interleukin-1β IPEX syndrome: immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome IQR: interquartile range LCH: Langerhans cell histiocytosis NEC: neonatal necrotizing enterocolitis NLR: neutrophil-to-lymphocyte ratio SLE: systemic lupus erythematosus UC: Ulcerative colitis VEO-IBD: very early-onset IBD Declarations Conflict of interest The authors have no conflicts of interest to disclose. Consent to participate declaration Written informed consent was obtained from the parents of all individual participants included in the study. Funding This study was supported by National Natural Science Foundation of China (81701486), and Foundation of Science and Technology Commission of Shanghai Municipality (16ZR1428400). Author Contributions W. Y. and Y. W. developed the study design. Y. Y. and Y. T. collected the data and wrote the manuscript. Y. X., Y. C., H. F., and Q. W. analyzed the data. W. Y. and Y. W. also reviewed and modified the manuscript. All of the authors approved the manuscript to be published. References Edden Y, Shih SS, Wexner SD (2009) Solitary rectal ulcer syndrome and stercoral ulcers. Gastroenterol Clin North Am 38:541-545 Cai J, Li F, Zhou W, Luo HS (2007) Ileocecal ulcer in central China: case series. Dig Dis Sci 52:3169-3173 Lee YJ, Yang SK, Byeon JS, Myung SJ, Chang HS, Hong SS, Kim KJ, Lee GH, Jung HY, Hong WS, Kim JH, Min YI, Chang SJ, Yu CS (2006) Analysis of colonoscopic findings in the differential diagnosis between intestinal tuberculosis and Crohn's disease. 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Aliment Pharmacol Ther Ouahed J, Spencer E, Kotlarz D, Shouval DS, Kowalik M, Peng K, Field M, Grushkin-Lerner L, Pai SY, Bousvaros A, Cho J, Argmann C, Schadt E, McGovern DPB, Mokry M, Nieuwenhuis E, Clevers H, Powrie F, Uhlig H, Klein C, Muise A, Dubinsky M, Snapper SB (2020) Very Early Onset Inflammatory Bowel Disease: A Clinical Approach With a Focus on the Role of Genetics and Underlying Immune Deficiencies. Inflamm Bowel Dis 26:820-842 Ozen S, Sag E (2020) Childhood vasculitis. Rheumatology (Oxford) 59:iii95-iii100 Nambu R, Hagiwara SI, Kakuta F, Hara T, Shimizu H, Abukawa D, Iwama I, Kagimoto S, Arai K (2019) Current role of colonoscopy in infants and young children: a multicenter study. BMC Gastroenterol 19:149 Kuenzig ME, Fung SG, Marderfeld L, Mak JWY, Kaplan GG, Ng SC, Wilson DC, Cameron F, Henderson P, Kotze PG, Bhatti J, Fang V, Gerber S, Guay E, Kotteduwa Jayawarden S, Kadota L, Maldonado DF, Osei JA, Sandarage R, Stanton A, Wan M, Benchimol EI (2022) Twenty-first Century Trends in the Global Epidemiology of Pediatric-Onset Inflammatory Bowel Disease: Systematic Review. Gastroenterology 162:1147-1159.e1144 Oliveira SB, Monteiro IM (2017) Diagnosis and management of inflammatory bowel disease in children. Bmj 357:j2083 Levine A, Koletzko S, Turner D, Escher JC, Cucchiara S, de Ridder L, Kolho KL, Veres G, Russell RK, Paerregaard A, Buderus S, Greer ML, Dias JA, Veereman-Wauters G, Lionetti P, Sladek M, Martin de Carpi J, Staiano A, Ruemmele FM, Wilson DC (2014) ESPGHAN revised porto criteria for the diagnosis of inflammatory bowel disease in children and adolescents. J Pediatr Gastroenterol Nutr 58:795-806 Huang B, Chen Z, Geng L, Wang J, Liang H, Cao Y, Chen H, et al. (2019) Mucosal Profiling of Pediatric-Onset Colitis and IBD Reveals Common Pathogenics and Therapeutic Pathways. Cell 179:1160-1176.e1124 Şimşek-Onat P, Hizarcioglu-Gulsen H, Ergen YM, Gumus E, Özen H, Demir H, Özen S, Saltık-Temizel İ N (2023) Neutrophil-to-Lymphocyte Ratio: An Easy Marker for the Diagnosis and Monitoring of Inflammatory Bowel Disease in Children. Dig Dis Sci 68:233-239 Fu W, Fu H, Ye W, Han Y, Liu X, Zhu S, Li H, Tang R, Wang Q (2021) Peripheral blood neutrophil-to-lymphocyte ratio in inflammatory bowel disease and disease activity: A meta-analysis. Int Immunopharmacol 101:108235 Zahmatkesh A, Sohouli MH, Hosseini SME, Rohani P (2023) The role of platelet-to-lymphocyte ratio and neutrophil-to-lymphocyte ratio in the diagnosis and severity of inflammatory bowel disease in children. Eur J Pediatr 182:4263-4270 Ricciuto A, Griffiths AM (2019) Clinical value of fecal calprotectin. Crit Rev Clin Lab Sci 56:307-320 Lężyk-Ciemniak E, Tworkiewicz M, Wilczyńska D, Szaflarska-Popławska A, Krogulska A (2021) Usefulness of Testing for Fecal Calprotectin in Pediatric Gastroenterology Clinical Practice. Med Princ Pract 30:311-319 Rengarajan S, Vivio EE, Parkes M, Peterson DA, Roberson EDO, Newberry RD, Ciorba MA, Hsieh CS (2020) Dynamic immunoglobulin responses to gut bacteria during inflammatory bowel disease. Gut Microbes 11:405-420 Aschenbrenner D, Quaranta M, Banerjee S, Ilott N, Jansen J, Steere B, Chen YH, Ho S, Cox K, Arancibia-Cárcamo CV, Coles M, Gaffney E, Travis SP, Denson L, Kugathasan S, Schmitz J, Powrie F, Sansom SN, Uhlig HH (2021) Deconvolution of monocyte responses in inflammatory bowel disease reveals an IL-1 cytokine network that regulates IL-23 in genetic and acquired IL-10 resistance. Gut 70:1023-1036 Bauer C, Duewell P, Mayer C, Lehr HA, Fitzgerald KA, Dauer M, Tschopp J, Endres S, Latz E, Schnurr M (2010) Colitis induced in mice with dextran sulfate sodium (DSS) is mediated by the NLRP3 inflammasome. Gut 59:1192-1199 Man SM (2018) Inflammasomes in the gastrointestinal tract: infection, cancer and gut microbiota homeostasis. Nat Rev Gastroenterol Hepatol 15:721-737 Peyrin-Biroulet L, Deltenre P, de Suray N, Branche J, Sandborn WJ, Colombel JF (2008) Efficacy and safety of tumor necrosis factor antagonists in Crohn's disease: meta-analysis of placebo-controlled trials. Clin Gastroenterol Hepatol 6:644-653 Additional Declarations No competing interests reported. Supplementary Files Supplementarymaterials.docx Cite Share Download PDF Status: Published Journal Publication published 01 Nov, 2024 Read the published version in BMC Pediatrics → Version 1 posted Editorial decision: Revision requested 19 Jul, 2024 Reviews received at journal 17 Jul, 2024 Reviews received at journal 08 Jul, 2024 Reviewers agreed at journal 01 Jul, 2024 Reviewers agreed at journal 30 Jun, 2024 Reviewers invited by journal 28 Jun, 2024 Editor invited by journal 26 Jun, 2024 Editor assigned by journal 20 Jun, 2024 Submission checks completed at journal 20 Jun, 2024 First submitted to journal 19 Jun, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4603636","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":324275583,"identity":"c65aa417-803a-45b2-836b-d5cfc1a31202","order_by":0,"name":"Yaying You","email":"","orcid":"","institution":"Division of Pediatric Gastroenterology and Nutrition, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Yaying","middleName":"","lastName":"You","suffix":""},{"id":324275584,"identity":"b7d6f680-070e-4dd5-807c-0d49f36637b0","order_by":1,"name":"Yijing Tao","email":"","orcid":"","institution":"Division of Pediatric Gastroenterology and Nutrition, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Yijing","middleName":"","lastName":"Tao","suffix":""},{"id":324275586,"identity":"38d8157a-a9d6-4a26-8bb0-221f8ab99587","order_by":2,"name":"Yanwen Xu","email":"","orcid":"","institution":"Division of Pediatric Gastroenterology and Nutrition, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Yanwen","middleName":"","lastName":"Xu","suffix":""},{"id":324275588,"identity":"800a34c6-e8bd-4f1b-97f2-b1c3f5f82673","order_by":3,"name":"Yi Cao","email":"","orcid":"","institution":"Division of Pediatric Gastroenterology and Nutrition, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Yi","middleName":"","lastName":"Cao","suffix":""},{"id":324275590,"identity":"a257f0c4-4cfd-427f-8a15-9cdd9b192eff","order_by":4,"name":"Haixia Feng","email":"","orcid":"","institution":"Division of Pediatric Gastroenterology and Nutrition, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Haixia","middleName":"","lastName":"Feng","suffix":""},{"id":324275592,"identity":"3b4f027d-2379-4e98-84d3-060321d9e071","order_by":5,"name":"Qingqing Wu","email":"","orcid":"","institution":"Division of Pediatric Gastroenterology and Nutrition, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Qingqing","middleName":"","lastName":"Wu","suffix":""},{"id":324275593,"identity":"3b5f3ac5-f6e2-43e1-a106-7d2086830a02","order_by":6,"name":"Ying Wang","email":"","orcid":"","institution":"Division of Pediatric Gastroenterology and Nutrition, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Ying","middleName":"","lastName":"Wang","suffix":""},{"id":324275594,"identity":"07f2c23b-180c-4bd7-9c85-f03cd10ab265","order_by":7,"name":"Yan Weihui","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABCklEQVRIiWNgGAWjYNACgwMMbOwNDAcYGyBcIrXwHCBJC8MBBgaJBAYGorQYHD97TOJDwZ3EPsk3hocLdxyW121v3sDwo2IbA//sBuxazuSlSc4weJbYJp2WcHjmmcOG284cK2DsOXObQeLOARy+yDG7zWNwGKgl+cBh3rbDjNtu5BgwM7bdZjAAORWblvNvzG7/AWmRPNgA0mK/7f4bAlpuAG1hAGmRYAbbkrjtBg9+LZI33pj/7DE4bNzGA/QLb1t68rYzaQUHgX7hkbiBXQvf+Rxjgx9/DsvObz9j/Jm3zdp22/HDGx/8qLgtxz8DuxYFrKECEuTBqh4I5BtwyYyCUTAKRsEogAEAD5Rs62raqPMAAAAASUVORK5CYII=","orcid":"","institution":"Division of Pediatric Gastroenterology and Nutrition, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine","correspondingAuthor":true,"prefix":"","firstName":"Yan","middleName":"","lastName":"Weihui","suffix":""}],"badges":[],"createdAt":"2024-06-19 06:25:39","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4603636/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4603636/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12887-024-05174-3","type":"published","date":"2024-11-01T15:57:22+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":60615350,"identity":"e7e9f7f9-0e2d-4871-9f57-a59e14986b11","added_by":"auto","created_at":"2024-07-18 20:11:52","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":23423055,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eEndoscopic figures of patients with different diagnosis in colon.\u003c/strong\u003e \u003cstrong\u003e(A)\u003c/strong\u003e UC: multiple continuous shallow ulcers with white coating on the surface. \u003cstrong\u003e(B)\u003c/strong\u003eCD: Cobblestone appearance with ulceration. \u003cstrong\u003e(C)\u003c/strong\u003e monogenic IBD-like disorder: Ulcerative lesions covered with pus coating, and accompanied by scattered inflammatory polypoid hyperplasia around the ulcer. \u003cstrong\u003e(D)\u003c/strong\u003e FPIES: clear multiple ulcers.\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-4603636/v1/8818c031de349f67ccdce100.png"},{"id":60614502,"identity":"53b242ed-0ef5-4c0d-a853-03ac75d1a8cd","added_by":"auto","created_at":"2024-07-18 20:03:52","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":60036402,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eRepresentative images of H\u0026amp;E staining for colon tissues of patients with different diagnosis. (A)\u003c/strong\u003eUC: formation of crypt abscess with partial gland deformation (200×). \u003cstrong\u003e(B)\u003c/strong\u003eCD: acute and chronic inflammatory cell aggregation (200×). \u003cstrong\u003e(C)\u003c/strong\u003emonogenic IBD-like disorder: infiltration of plasma cells and neutrophils, occasional crypt abscess (200×). \u003cstrong\u003e(D)\u003c/strong\u003e The figure of the child with FPIES: numerous eosinophils (200×).\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-4603636/v1/3c024be0db4cb93de2825f4b.png"},{"id":68207258,"identity":"9ad18d35-581b-4abe-9eb0-233a8ddaa047","added_by":"auto","created_at":"2024-11-04 16:36:14","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":198347889,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4603636/v1/d80432a7-d0a3-4da5-a241-e3ce606b98e7.pdf"},{"id":60614499,"identity":"fca9afd2-1e62-4ccc-9285-3eb4d05dd874","added_by":"auto","created_at":"2024-07-18 20:03:52","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":54305,"visible":true,"origin":"","legend":"","description":"","filename":"Supplementarymaterials.docx","url":"https://assets-eu.researchsquare.com/files/rs-4603636/v1/baae6ffa42e6a6afc3f62baa.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Clinical Analysis and Identification of Pediatric Patients with Colonic Ulceration","fulltext":[{"header":"What is known: ","content":"\u003cul start=\"12\"\u003e\n \u003cli\u003eMany diseases can mimic IBD and reducing the misdiagnosis of IBD children is essential for the treatment and prognosis.\u003c/li\u003e\n \u003cli\u003eInflammatory factors like erythrocyte sedimentation rate, and fecal calprotectin have clinical value in diagnosing IBD.\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003e\u003cstrong\u003eWhat is new:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cul\u003e\n \u003cli\u003eIn our study, we investigated that IBD was just responsible for 43% of patients with colonic ulceration.\u003c/li\u003e\n \u003cli\u003eSome potential indicators (like platelet, neutrophil-to-lymphocyte ratio and ulcer distribution character) may contribute to the diagnosis of pediatric IBD with colonic ulcers.\u003c/li\u003e\n\u003c/ul\u003e"},{"header":"Introduction","content":"\u003cp\u003eColonic ulcerations are a kind of localized defect of mucosal surface tissue found in colon and rectum[1]. The etiology of colonic ulceration is multiple, including inflammatory bowel disease (IBD), infectious colitis, allergic colitis, et al.[2-5]. Therefore, a differential diagnosis is required for further treatment and prognosis evaluation[6]. It is challenging, and misdiagnosis is not rare in clinical practice. Many diseases (including infection, drug-induced disease, vascular disorders, diverticular disease, diversion proctocolitis, and immune disorders) can mimic IBD in clinical and pathological features[7]. Inflammatory factors like erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and fecal calprotectin (FCP) have been found to have potential clinical diagnosis value with IBD but still need higher specificity[8,9]. In most cases, acute infectious colitis is easily identified by clinical symptoms with no requirement for colonoscopy. But the patients with negative findings in pathogen tests, who present gastrointestinal bleeding, respond poorly to treatment or have previous chronic gastrointestinal disorders, may undergo colonoscopic examination and confront the complex differential diagnosis[10]. Gastrointestinal-involved vasculitis, such as immunoglobulin A vasculitis and systemic lupus erythematosus (SLE), could be very similar to IBD in the symptoms, endoscopic findings, and histological assessment. European Crohn\u0026apos;s and Colitis Organisation (ECCO) recommended some features to help in the differential diagnosis between primary vasculitis and IBD[7]. The imaging, serological, fecal, and molecular tests could assist differentiation.\u003c/p\u003e\n\u003cp\u003eThe manifestation of IBD in the pediatric population is more complicated and less specific than in adults for a higher ratio of genetic factors involved. It is well-known that IBD is diagnosed based on an exclusive method. Therefore, it is prone to be overdiagnosed in patients with colonic ulceration[1,2,11]. Pediatricians should also pay attention to gastrointestinal allergic diseases, which are more prevalent in children and increasing[12]. The data focused on the pediatric population is limited. To avoid diagnostic pitfalls, we observed the colonoscopy findings of ulcer features and combined them with the clinical manifestations and biochemical indexes of patients for the further recognition of related diseases, especially between IBD and non-IBD diseases. We summarized the differential manifestations of patients in the study and hoped to provide an alert for the misdiagnosis of children with colonic ulceration.\u003c/p\u003e"},{"header":"Materials And Methods","content":"\u003cp\u003e\u003cstrong\u003e2.1 Patients and Study Design\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFrom December 2014 to June 2022, 86 pediatric patients (age from 1 month to 15 years, and male: female = 42: 44) were analyzed in the study from Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine. Inpatients with colonic ulceration discovered by colonoscopy for the first time were eligible for the inclusion criteria. The patients with ulcers that are isolated in rectum were excluded. All children had relatively complete medical history records.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eDemographic parameters, clinical characteristics, and laboratory examinations were collected from the medical record retrieval system. Demographic parameters included age and gender. Clinical characteristics harbored weight loss/failure to thrive, abdominal pain, diarrhea, constipation, hematochezia, fever, perianal lesions, rash, oral ulcer, and joint pain. The colonoscopy findings were analyzed retrospectively in combination with histopathological results. Furthermore, we divided the lower gastrointestinal tract into terminal ileum, ileocecal part, ascending colon, transverse colon, descending colon, sigmoid colon and rectum; every part with ulceration meant one score, and then we accumulated total score. The etiology was determined by clinical manifestation, examination, and long-term follow-up. The IBD was diagnosed after excluding infectious, allergic, immunologic and other diseases. When genetic mutation associated with the primary immune deficiencies was detected, we diagnosed those patients as monogenic IBD-like disorders but not ulcerative colitis (UC) or Crohn\u0026apos;s disease (CD) in this study[7]. Nonspecific colonic ulcer was diagnosed in the patients who ruled out other diseases and recovered well without any treatment during the follow-up.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.2 Statistical analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll data were analyzed using SPSS 26.0 (SPSS, Inc., IBM, Chicago, Illinois, USA). The measurement data were expressed using a median with an interquartile range (IQR). The enumeration data were presented by frequency or proportions. Mann\u0026ndash;Whitney non-parametric test, Pearson\u0026rsquo;s chi-squared test or Fisher\u0026rsquo;s exact test were used for the comparison between different groups. A \u003cem\u003eP\u003c/em\u003e value \u0026lt; 0.05 was defined as the statistical significance.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.3 Ethics approval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn accordance with the Declaration of Helsinki, the study was approved by the Ethics Committee of Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (XHEC-D-2022-250).\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003e3.1 The diagnosis of children finding colonic ulcer\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEighty-six pediatric patients finding colonic ulcers were enrolled in the research. Etiological analysis of patients was shown in Table 1. Of note, the most common diagnosis was IBD (37/86), including UC (8/86, 9.3%), CD (22/86, 25.6%), and Monogenic IBD-like disorders (7/86, 8.1%) with the mutation of \u003cem\u003eIL10RA\u003c/em\u003e, \u003cem\u003eEP300\u003c/em\u003e mutation, \u003cem\u003ePIK3CD\u003c/em\u003e mutation, Wiskott-Aldrich Syndrome, and immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome, respectively. Otherwise, there were autoimmune diseases (6 cases of IgA vasculitis (7.0%), 2 cases of other vasculitis (2.3%), and 1 case of SLE (1.2%), respectively), and gastrointestinal allergy (2 cases of food protein-induced enterocolitis (FPIES) (2.3%), 3 cases of eosinophilic gastroenteritis (3.5%), and 3 cases of other gastrointestinal allergy diseases (3.5%), respectively). A high ratio of children was also diagnosed with infectious enteritis (13/86, 15.1%). Other causes of colonic ulcers included nonspecific colonic ulcers (14/86, 16.3%), neonatal necrotizing enterocolitis (NEC) (1, 1.2%), Hirschsprung\u0026rsquo;s disease (1, 1.2%), Langerhans cell histiocytosis (LCH) (1, 1.2%), Digestive perianastomotic ulcerations (1, 1.2%), and anal fistula (1, 1.2%).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 1 Etiological analysis of patients\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;with colonic ulceration.\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"576\"\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003ctd width=\"73.78472222222223%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eEtiology\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.21527777777778%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eNumber (n = 86)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"73.78472222222223%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eIBD (n= 37)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.21527777777778%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"73.78472222222223%\" valign=\"top\"\u003e\n \u003cp\u003e*UC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.21527777777778%\" valign=\"top\"\u003e\n \u003cp\u003e8 (9.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"73.78472222222223%\" valign=\"top\"\u003e\n \u003cp\u003e*CD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.21527777777778%\" valign=\"top\"\u003e\n \u003cp\u003e22 (25.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"73.78472222222223%\" valign=\"top\"\u003e\n \u003cp\u003eMonogenic IBD-like disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.21527777777778%\" valign=\"top\"\u003e\n \u003cp\u003e7 (8.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"73.78472222222223%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eNon-IBD (n= 49)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.21527777777778%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"73.78472222222223%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eAutoimmune diseases\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.21527777777778%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"73.78472222222223%\" valign=\"top\"\u003e\n \u003cp\u003eVasculitis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.21527777777778%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"73.78472222222223%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;IgA vasculitis (Henoch-Sch\u0026ouml;nlein purpura)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.21527777777778%\" valign=\"top\"\u003e\n \u003cp\u003e6 (7.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"73.78472222222223%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Other vasculitis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.21527777777778%\" valign=\"top\"\u003e\n \u003cp\u003e2 (2.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"73.78472222222223%\" valign=\"top\"\u003e\n \u003cp\u003eSLE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.21527777777778%\" valign=\"top\"\u003e\n \u003cp\u003e1 (1.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"73.78472222222223%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eInfectious enteritis\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.21527777777778%\" valign=\"top\"\u003e\n \u003cp\u003e13 (15.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"73.78472222222223%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eGastrointestinal allergy\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.21527777777778%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"73.78472222222223%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; FPIES\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.21527777777778%\" valign=\"top\"\u003e\n \u003cp\u003e2 (2.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"73.78472222222223%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; Eosinophilic gastroenteritis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.21527777777778%\" valign=\"top\"\u003e\n \u003cp\u003e3 (3.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"73.78472222222223%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; Other gastrointestinal allergy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.21527777777778%\" valign=\"top\"\u003e\n \u003cp\u003e3 (3.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"73.78472222222223%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eOthers\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.21527777777778%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"73.78472222222223%\" valign=\"top\"\u003e\n \u003cp\u003eNonspecific colonic ulcer\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.21527777777778%\" valign=\"top\"\u003e\n \u003cp\u003e14 (16.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"73.78472222222223%\" valign=\"top\"\u003e\n \u003cp\u003eNEC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.21527777777778%\" valign=\"top\"\u003e\n \u003cp\u003e1 (1.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"73.78472222222223%\" valign=\"top\"\u003e\n \u003cp\u003eHirschsprung\u0026rsquo;s disease\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.21527777777778%\" valign=\"top\"\u003e\n \u003cp\u003e1 (1.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"73.78472222222223%\" valign=\"top\"\u003e\n \u003cp\u003eLCH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.21527777777778%\" valign=\"top\"\u003e\n \u003cp\u003e1 (1.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"73.78472222222223%\" valign=\"top\"\u003e\n \u003cp\u003eDigestive perianastomotic ulcerations\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.21527777777778%\" valign=\"top\"\u003e\n \u003cp\u003e1 (1.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"73.78472222222223%\" valign=\"top\"\u003e\n \u003cp\u003eAnal\u0026nbsp;Fistula\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.21527777777778%\" valign=\"top\"\u003e\n \u003cp\u003e1 (1.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eIBD = Inflammatory bowel disease, *UC = Ulcerative colitis with no monogenic abnormality, *CD = Crohn\u0026apos;s disease with no monogenic abnormality, SLE = Systemic lupus erythematosus, FPIES = Food protein-induced enterocolitis, NEC = Neonatal necrotizing enterocolitis, LCH = Langerhans cell histiocytosis\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003e3.2 Comparison of clinical characteristics in patients with colonic ulceration\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eChildren were divided into IBD (n = 37) and non-IBD (n = 49) groups for further exploring the potential specific indicators of IBD. Statistical analysis displayed no significant difference between IBD and non-IBD groups in age and gender. The frequency of weight loss/failure to thrive (\u003cem\u003eP\u003c/em\u003e \u0026lt; 0.001), perianal lesions (\u003cem\u003eP\u003c/em\u003e =0.001), and oral ulcer (\u003cem\u003eP\u003c/em\u003e = 0.022) was significantly higher in IBD group than in non-IBD group (Table 2). The frequency of fever is higher in IBD group (18, 48.6%) than in non-IBD group (14, 28.6%), even though there was no significant difference between two groups (\u003cem\u003eP\u003c/em\u003e = 0.057).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThen, we further divided children into Normal IBD (UC or CD with no monogenic abnormality)，\u0026nbsp;Monogenic IBD-like disorders and non-IBD groups (Table S1 \u0026ndash; S3). Statistical analysis showed that the age of children with monogenic IBD-like disorders is significantly younger than children in Normal IBD or non-IBD groups (\u003cem\u003eP\u003c/em\u003e \u0026lt; 0.001).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2 Comparison of characteristics of IBD and non-IBD patients.\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"576\"\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.25%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eEvents\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.395833333333332%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eIBD\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(n = 37), n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.34722222222222%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eNon-IBD\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(n = 49), n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.01388888888889%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eP\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"3.9930555555555554%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.25%\" valign=\"top\"\u003e\n \u003cp\u003eAge, y,\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.395833333333332%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.34722222222222%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.01388888888889%\" valign=\"top\"\u003e\n \u003cp\u003e0.115\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"3.9930555555555554%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.25%\" valign=\"top\"\u003e\n \u003cp\u003eage \u0026lt; 2 y\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.395833333333332%\" valign=\"top\"\u003e\n \u003cp\u003e8 (21.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.34722222222222%\" valign=\"top\"\u003e\n \u003cp\u003e11 (22.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.01388888888889%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"3.9930555555555554%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.25%\" valign=\"top\"\u003e\n \u003cp\u003e2 y \u0026le; age \u0026lt; 6 y\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.395833333333332%\" valign=\"top\"\u003e\n \u003cp\u003e3 (8.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.34722222222222%\" valign=\"top\"\u003e\n \u003cp\u003e9 (18.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.01388888888889%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"3.9930555555555554%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.25%\" valign=\"top\"\u003e\n \u003cp\u003e6 y \u0026le; age \u0026lt; 10 y\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.395833333333332%\" valign=\"top\"\u003e\n \u003cp\u003e8 (21.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.34722222222222%\" valign=\"top\"\u003e\n \u003cp\u003e16 (32.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.01388888888889%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"3.9930555555555554%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.25%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;Age \u0026ge; 10 y\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.395833333333332%\" valign=\"top\"\u003e\n \u003cp\u003e18 (48.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.34722222222222%\" valign=\"top\"\u003e\n \u003cp\u003e13 (26.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.01388888888889%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"3.9930555555555554%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.25%\" valign=\"top\"\u003e\n \u003cp\u003eGender (Male/Female)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.395833333333332%\" valign=\"top\"\u003e\n \u003cp\u003e16/21\u003c/p\u003e\n \u003cp\u003e(43.2%/56.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.34722222222222%\" valign=\"top\"\u003e\n \u003cp\u003e26/23\u003c/p\u003e\n \u003cp\u003e(53.1%/46.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.01388888888889%\" valign=\"top\"\u003e\n \u003cp\u003e0.367\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"3.9930555555555554%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.25%\" valign=\"top\"\u003e\n \u003cp\u003eAbnormal\u0026nbsp;findings\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.395833333333332%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.34722222222222%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.01388888888889%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"3.9930555555555554%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.25%\" valign=\"top\"\u003e\n \u003cp\u003eWeight loss/failure to thrive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.395833333333332%\" valign=\"top\"\u003e\n \u003cp\u003e16 (43.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.34722222222222%\" valign=\"top\"\u003e\n \u003cp\u003e6 (12.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.01388888888889%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001***\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"3.9930555555555554%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.25%\" valign=\"top\"\u003e\n \u003cp\u003eAbdominal pain\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.395833333333332%\" valign=\"top\"\u003e\n \u003cp\u003e17 (45.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.34722222222222%\" valign=\"top\"\u003e\n \u003cp\u003e33 (67.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.006944444444443%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.046*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.25%\" valign=\"top\"\u003e\n \u003cp\u003eDiarrhea\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.395833333333332%\" valign=\"top\"\u003e\n \u003cp\u003e19 (51.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.34722222222222%\" valign=\"top\"\u003e\n \u003cp\u003e20 (40.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.01388888888889%\" valign=\"top\"\u003e\n \u003cp\u003e0.331\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"3.9930555555555554%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.25%\" valign=\"top\"\u003e\n \u003cp\u003eConstipation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.395833333333332%\" valign=\"top\"\u003e\n \u003cp\u003e4 (10.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.34722222222222%\" valign=\"top\"\u003e\n \u003cp\u003e6 (12.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.01388888888889%\" valign=\"top\"\u003e\n \u003cp\u003e1.000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"3.9930555555555554%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.25%\" valign=\"top\"\u003e\n \u003cp\u003eHematochezia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.395833333333332%\" valign=\"top\"\u003e\n \u003cp\u003e15 (40.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.34722222222222%\" valign=\"top\"\u003e\n \u003cp\u003e25 (51.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.01388888888889%\" valign=\"top\"\u003e\n \u003cp\u003e0.335\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"3.9930555555555554%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.25%\" valign=\"top\"\u003e\n \u003cp\u003eFever\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.395833333333332%\" valign=\"top\"\u003e\n \u003cp\u003e18 (48.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.34722222222222%\" valign=\"top\"\u003e\n \u003cp\u003e14 (28.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.01388888888889%\" valign=\"top\"\u003e\n \u003cp\u003e0.057\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"3.9930555555555554%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.25%\" valign=\"top\"\u003e\n \u003cp\u003ePerianal lesions\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.395833333333332%\" valign=\"top\"\u003e\n \u003cp\u003e13 (35.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.34722222222222%\" valign=\"top\"\u003e\n \u003cp\u003e3 (6.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.01388888888889%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.001**\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"3.9930555555555554%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.25%\" valign=\"top\"\u003e\n \u003cp\u003eRash\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.395833333333332%\" valign=\"top\"\u003e\n \u003cp\u003e7 (18.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.34722222222222%\" valign=\"top\"\u003e\n \u003cp\u003e8(16.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.01388888888889%\" valign=\"top\"\u003e\n \u003cp\u003e0.754\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"3.9930555555555554%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.25%\" valign=\"top\"\u003e\n \u003cp\u003eOral ulcer\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.395833333333332%\" valign=\"top\"\u003e\n \u003cp\u003e7 (18.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.34722222222222%\" valign=\"top\"\u003e\n \u003cp\u003e1 (2.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.01388888888889%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.022*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"3.9930555555555554%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.25%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;Joint pain\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.395833333333332%\" valign=\"top\"\u003e\n \u003cp\u003e4 (10.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.34722222222222%\" valign=\"top\"\u003e\n \u003cp\u003e2 (4.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.01388888888889%\" valign=\"top\"\u003e\n \u003cp\u003e0.432\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"3.9930555555555554%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eIBD = Inflammatory bowel disease. *\u003cem\u003eP\u003c/em\u003e \u0026lt;0.05, **\u003cem\u003eP\u003c/em\u003e \u0026lt;0.01, ***\u003cem\u003eP\u003c/em\u003e \u0026lt;0.001\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.3 Comparison of biochemical indexes in patients with colonic ulceration\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe biochemical indexes were then analyzed in different groups (Table 3, Table S4 \u0026ndash; S6). The levels of hemoglobin (\u003cem\u003eP\u003c/em\u003e \u0026lt; 0.001) and albumin (\u003cem\u003eP\u003c/em\u003e = 0.001) were lower in IBD group than in non-IBD group, While the levels of platelet (\u003cem\u003eP\u003c/em\u003e = 0.006), neutrophil-to-lymphocyte ratio (NLR) (\u003cem\u003eP\u003c/em\u003e \u0026lt; 0.001), ESR (\u003cem\u003eP\u003c/em\u003e \u0026lt; 0.001), CRP (\u003cem\u003eP\u003c/em\u003e \u0026lt; 0.001), Immunoglobulin G (IgG) (\u003cem\u003eP\u003c/em\u003e = 0.012), and Interleukin-1\u0026beta; (IL-1\u0026beta;) (\u003cem\u003eP\u003c/em\u003e = 0.003), IL-6 (\u003cem\u003eP\u003c/em\u003e = 0.024) and TNF-\u0026alpha; (\u003cem\u003eP\u003c/em\u003e = 0.026) were significantly higher in IBD group than in non-IBD group. In addition, the level of FCP was \u0026gt; 1500 ug/g in 22 cases (78.6%) of IBD children and in 14 cases (58.3%) of non-IBD children (\u003cem\u003eP\u003c/em\u003e = 0.065) (Table 3). NLR, ESR, CRP and TNF-\u0026alpha; showed higher level in CD group than in gastrointestinal allergy group (Table S6).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3 Comparison of biochemical indexes of IBD and non-IBD patients.\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"576\"\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.8125%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eEvents\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.916666666666668%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eIBD\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(n = 37)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.21527777777778%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eNon-IBD\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(n = 49)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.055555555555557%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eP\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.8125%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;Hemoglobin, g/dL,\u0026nbsp;\u003c/p\u003e\n \u003cp\u003en, median (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.916666666666668%\" valign=\"top\"\u003e\n \u003cp\u003e37, 109.00\u003c/p\u003e\n \u003cp\u003e(87.50 - 121.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.21527777777778%\" valign=\"top\"\u003e\n \u003cp\u003e49, 127.00\u003c/p\u003e\n \u003cp\u003e(111.50 - 132.50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.055555555555557%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001***\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.8125%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;Albumin, mg/dL\u0026nbsp;\u003c/p\u003e\n \u003cp\u003en, median (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.916666666666668%\" valign=\"top\"\u003e\n \u003cp\u003e37, 36.60\u003c/p\u003e\n \u003cp\u003e(31.45 - 41.25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.21527777777778%\" valign=\"top\"\u003e\n \u003cp\u003e49, 42.60\u003c/p\u003e\n \u003cp\u003e(37.20 - 45.55)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.055555555555557%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.001**\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.8125%\" valign=\"top\"\u003e\n \u003cp\u003ePlatelet, 10^9/L\u003c/p\u003e\n \u003cp\u003en, median (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.916666666666668%\" valign=\"top\"\u003e\n \u003cp\u003e37, 397\u003c/p\u003e\n \u003cp\u003e(310 - 521)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.21527777777778%\" valign=\"top\"\u003e\n \u003cp\u003e49, 302\u003c/p\u003e\n \u003cp\u003e(258 - 391)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.055555555555557%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.006**\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.8125%\" valign=\"top\"\u003e\n \u003cp\u003eD-Dimer\u003c/p\u003e\n \u003cp\u003en, median (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.916666666666668%\" valign=\"top\"\u003e\n \u003cp\u003e29, 0.55\u003c/p\u003e\n \u003cp\u003e(0.32 - 0.86)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.21527777777778%\" valign=\"top\"\u003e\n \u003cp\u003e42, 0.315\u003c/p\u003e\n \u003cp\u003e(0.23 \u0026ndash; 0.827)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.055555555555557%\" valign=\"top\"\u003e\n \u003cp\u003e0.124\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.8125%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;NLR\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;n, median (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.916666666666668%\" valign=\"top\"\u003e\n \u003cp\u003e37, 2.49\u003c/p\u003e\n \u003cp\u003e(1.80 - 4.42)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.21527777777778%\" valign=\"top\"\u003e\n \u003cp\u003e49, 1.41\u003c/p\u003e\n \u003cp\u003e(0.96 - 2.70)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.055555555555557%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.001**\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.8125%\" valign=\"top\"\u003e\n \u003cp\u003eAST, U/L\u003c/p\u003e\n \u003cp\u003en, median (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.916666666666668%\" valign=\"top\"\u003e\n \u003cp\u003e37, 29.00\u003c/p\u003e\n \u003cp\u003e(19.85 - 40.50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.21527777777778%\" valign=\"top\"\u003e\n \u003cp\u003e49, 34.00\u003c/p\u003e\n \u003cp\u003e(25.35 - 42.15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.055555555555557%\" valign=\"top\"\u003e\n \u003cp\u003e0.081\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.8125%\" valign=\"top\"\u003e\n \u003cp\u003eALT, U/L\u003c/p\u003e\n \u003cp\u003en, median (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.916666666666668%\" valign=\"top\"\u003e\n \u003cp\u003e37, 16.00\u003c/p\u003e\n \u003cp\u003e(10.00 - 21.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.21527777777778%\" valign=\"top\"\u003e\n \u003cp\u003e49, 19.00\u003c/p\u003e\n \u003cp\u003e(11.00 - 26.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.055555555555557%\" valign=\"top\"\u003e\n \u003cp\u003e0.230\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.8125%\" valign=\"top\"\u003e\n \u003cp\u003eESR, mm/h,\u0026nbsp;\u003c/p\u003e\n \u003cp\u003en, median (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.916666666666668%\" valign=\"top\"\u003e\n \u003cp\u003e36, 36.50\u003c/p\u003e\n \u003cp\u003e(20.50 \u0026ndash; 64.25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.21527777777778%\" valign=\"top\"\u003e\n \u003cp\u003e33, 16.00\u003c/p\u003e\n \u003cp\u003e(2.50 \u0026ndash; 26.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.055555555555557%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001***\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.8125%\" valign=\"top\"\u003e\n \u003cp\u003eCRP, mg/L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.916666666666668%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.21527777777778%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.055555555555557%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001***\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.8125%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;8, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.916666666666668%\" valign=\"top\"\u003e\n \u003cp\u003e10 (27.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.21527777777778%\" valign=\"top\"\u003e\n \u003cp\u003e33 (67.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.055555555555557%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.8125%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026ge;8, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.916666666666668%\" valign=\"top\"\u003e\n \u003cp\u003e27 (73.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.21527777777778%\" valign=\"top\"\u003e\n \u003cp\u003e16 (32.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.055555555555557%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.8125%\" valign=\"top\"\u003e\n \u003cp\u003ePositive fecal transferrin,\u0026nbsp;\u003c/p\u003e\n \u003cp\u003en (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.916666666666668%\" valign=\"top\"\u003e\n \u003cp\u003e16 (84.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.21527777777778%\" valign=\"top\"\u003e\n \u003cp\u003e27 (90.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.055555555555557%\" valign=\"top\"\u003e\n \u003cp\u003e0.877\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.8125%\" valign=\"top\"\u003e\n \u003cp\u003ePositive fecal occult blood,\u003c/p\u003e\n \u003cp\u003en (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.916666666666668%\" valign=\"top\"\u003e\n \u003cp\u003e21 (60.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.21527777777778%\" valign=\"top\"\u003e\n \u003cp\u003e28 (62.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.055555555555557%\" valign=\"top\"\u003e\n \u003cp\u003e0.840\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.8125%\" valign=\"top\"\u003e\n \u003cp\u003eFCP, ug/g\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.916666666666668%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.21527777777778%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.055555555555557%\" valign=\"top\"\u003e\n \u003cp\u003e0.065\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.8125%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026le; 50, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.916666666666668%\" valign=\"top\"\u003e\n \u003cp\u003e1 (3.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.21527777777778%\" valign=\"top\"\u003e\n \u003cp\u003e2 (8.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.055555555555557%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.8125%\" valign=\"top\"\u003e\n \u003cp\u003e50 \u0026lt; FCP \u0026le; 500, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.916666666666668%\" valign=\"top\"\u003e\n \u003cp\u003e1 (3.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.21527777777778%\" valign=\"top\"\u003e\n \u003cp\u003e6 (25%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.055555555555557%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.8125%\" valign=\"top\"\u003e\n \u003cp\u003e500 \u0026lt; FCP \u0026le; 1000, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.916666666666668%\" valign=\"top\"\u003e\n \u003cp\u003e2 (7.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.21527777777778%\" valign=\"top\"\u003e\n \u003cp\u003e2 (8.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.055555555555557%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.8125%\" valign=\"top\"\u003e\n \u003cp\u003e1000 \u0026lt; FCP \u0026le; 1500, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.916666666666668%\" valign=\"top\"\u003e\n \u003cp\u003e2 (7.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.21527777777778%\" valign=\"top\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.055555555555557%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.8125%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026gt; 1500, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.916666666666668%\" valign=\"top\"\u003e\n \u003cp\u003e22 (78.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.21527777777778%\" valign=\"top\"\u003e\n \u003cp\u003e14 (58.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.055555555555557%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.8125%\" valign=\"top\"\u003e\n \u003cp\u003eIgA, g/L\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.916666666666668%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.21527777777778%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.055555555555557%\" valign=\"top\"\u003e\n \u003cp\u003e0.279\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.8125%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt; 0.7, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.916666666666668%\" valign=\"top\"\u003e\n \u003cp\u003e5 (17.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.21527777777778%\" valign=\"top\"\u003e\n \u003cp\u003e7 (26.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.055555555555557%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.8125%\" valign=\"top\"\u003e\n \u003cp\u003e0.7 \u0026le; IgA \u0026lt; 4, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.916666666666668%\" valign=\"top\"\u003e\n \u003cp\u003e20 (71.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.21527777777778%\" valign=\"top\"\u003e\n \u003cp\u003e18 (69.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.055555555555557%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.8125%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026ge; 4, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.916666666666668%\" valign=\"top\"\u003e\n \u003cp\u003e3 (10.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.21527777777778%\" valign=\"top\"\u003e\n \u003cp\u003e1 (3.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.055555555555557%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.8125%\" valign=\"top\"\u003e\n \u003cp\u003eIgG, g/L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.916666666666668%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.21527777777778%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.055555555555557%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.012*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.8125%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt; 7, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.916666666666668%\" valign=\"top\"\u003e\n \u003cp\u003e2 (7.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.21527777777778%\" valign=\"top\"\u003e\n \u003cp\u003e7 (26.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.055555555555557%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.8125%\" valign=\"top\"\u003e\n \u003cp\u003e7 \u0026le; IgG \u0026lt; 16, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.916666666666668%\" valign=\"top\"\u003e\n \u003cp\u003e20 (71.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.21527777777778%\" valign=\"top\"\u003e\n \u003cp\u003e18 (69.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.055555555555557%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.8125%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026ge; 16, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.916666666666668%\" valign=\"top\"\u003e\n \u003cp\u003e6 (21.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.21527777777778%\" valign=\"top\"\u003e\n \u003cp\u003e1 (3.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.055555555555557%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.8125%\" valign=\"top\"\u003e\n \u003cp\u003eIL-8, pg/mL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.916666666666668%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.21527777777778%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.055555555555557%\" valign=\"top\"\u003e\n \u003cp\u003e0.921\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.8125%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u0026lt; 62, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.916666666666668%\" valign=\"top\"\u003e\n \u003cp\u003e10 (43.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.21527777777778%\" valign=\"top\"\u003e\n \u003cp\u003e9 (45.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.055555555555557%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.8125%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u0026ge; 62, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.916666666666668%\" valign=\"top\"\u003e\n \u003cp\u003e13 (56.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.21527777777778%\" valign=\"top\"\u003e\n \u003cp\u003e11 (55.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.055555555555557%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.8125%\" valign=\"top\"\u003e\n \u003cp\u003eIL-1\u0026beta;, pg/mL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.916666666666668%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.21527777777778%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.055555555555557%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.003**\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.8125%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u0026lt; 5, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.916666666666668%\" valign=\"top\"\u003e\n \u003cp\u003e2 (8.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.21527777777778%\" valign=\"top\"\u003e\n \u003cp\u003e10 (50.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.055555555555557%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.8125%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u0026ge; 5, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.916666666666668%\" valign=\"top\"\u003e\n \u003cp\u003e21 (91.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.21527777777778%\" valign=\"top\"\u003e\n \u003cp\u003e10 (50.0%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.055555555555557%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.8125%\" valign=\"top\"\u003e\n \u003cp\u003eIL-6, pg/mL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.916666666666668%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.21527777777778%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.055555555555557%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.024*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.8125%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u0026lt; 5.9, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.916666666666668%\" valign=\"top\"\u003e\n \u003cp\u003e4 (17.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.21527777777778%\" valign=\"top\"\u003e\n \u003cp\u003e10 (50.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.055555555555557%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.8125%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u0026ge; 5.9, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.916666666666668%\" valign=\"top\"\u003e\n \u003cp\u003e19 (82.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.21527777777778%\" valign=\"top\"\u003e\n \u003cp\u003e10 (50.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.055555555555557%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.8125%\" valign=\"top\"\u003e\n \u003cp\u003eIL-10, pg/mL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.916666666666668%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.21527777777778%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.055555555555557%\" valign=\"top\"\u003e\n \u003cp\u003e0.988\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.8125%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u0026lt; 9.1, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.916666666666668%\" valign=\"top\"\u003e\n \u003cp\u003e15 (65.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.21527777777778%\" valign=\"top\"\u003e\n \u003cp\u003e13 (65.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.055555555555557%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.8125%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u0026ge; 9.1, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.916666666666668%\" valign=\"top\"\u003e\n \u003cp\u003e8 (34.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.21527777777778%\" valign=\"top\"\u003e\n \u003cp\u003e7 (35.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.055555555555557%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.8125%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;TNF-\u0026alpha;, pg/mL\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.916666666666668%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.21527777777778%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.055555555555557%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.026*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.8125%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u0026lt; 8.1, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.916666666666668%\" valign=\"top\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.21527777777778%\" valign=\"top\"\u003e\n \u003cp\u003e4 (20.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.055555555555557%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.8125%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u0026ge; 8.1, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.916666666666668%\" valign=\"top\"\u003e\n \u003cp\u003e23 (100.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.21527777777778%\" valign=\"top\"\u003e\n \u003cp\u003e16 (80.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.055555555555557%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.8125%\" valign=\"top\"\u003e\n \u003cp\u003eIL-2R, pg/mL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.916666666666668%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.21527777777778%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.055555555555557%\" valign=\"top\"\u003e\n \u003cp\u003e0.080\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.8125%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;710, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.916666666666668%\" valign=\"top\"\u003e\n \u003cp\u003e3 (12.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.21527777777778%\" valign=\"top\"\u003e\n \u003cp\u003e7 (35.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.055555555555557%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.8125%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026ge; 710, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.916666666666668%\" valign=\"top\"\u003e\n \u003cp\u003e21 (87.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.21527777777778%\" valign=\"top\"\u003e\n \u003cp\u003e13 (65.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.055555555555557%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.8125%\" valign=\"top\"\u003e\n \u003cp\u003e25-(OH)-VitD, nmol/L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.916666666666668%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.21527777777778%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.055555555555557%\" valign=\"top\"\u003e\n \u003cp\u003e0.142\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.8125%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026le; 50, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.916666666666668%\" valign=\"top\"\u003e\n \u003cp\u003e16 (80.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.21527777777778%\" valign=\"top\"\u003e\n \u003cp\u003e6 (54.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.055555555555557%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.8125%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026gt; 50, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.916666666666668%\" valign=\"top\"\u003e\n \u003cp\u003e4 (20.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.21527777777778%\" valign=\"top\"\u003e\n \u003cp\u003e5 (45.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.055555555555557%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eIBD = Inflammatory bowel disease, NLR = neutrophil-to-lymphocyte ratio, AST = Alanine aminotransferase, ALT = Alanine aminotransferase, ESR = Erythrocyte sedimentation rate, CRP = C-reactive protein, FCP = Fecal calprotectin, IgA = Immunoglobulin A, IgG = Immunoglobulin G, IL-8 = Interleukin-8, IL-1\u0026beta; = Interleukin-1\u0026beta;, IL-6 = Interleukin-6, IL-10 = Interleukin-10, TNF-\u0026alpha; = tumor necrosis factor-\u0026alpha;, IL-2R = Interleukin-2 receptor, 25-(OH)-VitD = 25-hydroxyvitamin D. *\u003cem\u003eP\u003c/em\u003e \u0026lt;0.05, **\u003cem\u003eP\u003c/em\u003e \u0026lt;0.01, ***\u003cem\u003eP\u003c/em\u003e \u0026lt;0.001\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003e3.4 The comparison of endoscopic characteristics in patients with colonic ulceration\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNext, we collected the endoscopic figures of patients with different diagnosis (UC, CD, monogenic IBD-like disorders and non-IBD, respectively) in Figure 1. We sorted out the endoscopic information of patients (Table 4, Table S7 - S8). The existence of upper gastrointestinal ulceration presented no significant difference in IBD and non-IBD groups. Colonoscopy revealed that ulcers could be found in any segment of the colon, and a wider ulcer distribution range in lower gastrointestinal tract was found in IBD group than in non-IBD group (\u003cem\u003eP\u003c/em\u003e \u0026lt; 0.001), especially between CD and infectious enteritis groups. Besides, Table 4 displayed that cobblestone appearance mainly showed in IBD group (\u003cem\u003eP\u003c/em\u003e = 0.031).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 4 Comparison of endoscopic characteristics in IBD and non-IBD patients.\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003ctd width=\"47.83393501805054%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eEvents\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.14801444043321%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eIBD\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(n = 37)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.967509025270758%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eNon-IBD\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(n = 49)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.050541516245488%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eP\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003evalue\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"47.83393501805054%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eUlcer distribution\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.14801444043321%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.967509025270758%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.050541516245488%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"47.83393501805054%\" valign=\"top\"\u003e\n \u003cp\u003eUpper gastrointestinal ulceration, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.14801444043321%\" valign=\"top\"\u003e\n \u003cp\u003e9 (24.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.967509025270758%\" valign=\"top\"\u003e\n \u003cp\u003e4(10.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.050541516245488%\" valign=\"top\"\u003e\n \u003cp\u003e0.104\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"47.83393501805054%\" valign=\"top\"\u003e\n \u003cp\u003e*Score of ulceration in lower GI,\u003c/p\u003e\n \u003cp\u003emedian (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.14801444043321%\" valign=\"top\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003cp\u003e(2 \u0026ndash; 6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.967509025270758%\" valign=\"top\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003cp\u003e(1 \u0026ndash; 2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.050541516245488%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001***\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"47.83393501805054%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eAbnormal findings\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.14801444043321%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.967509025270758%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.050541516245488%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"47.83393501805054%\" valign=\"top\"\u003e\n \u003cp\u003eErythema, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.14801444043321%\" valign=\"top\"\u003e\n \u003cp\u003e1 (2.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.967509025270758%\" valign=\"top\"\u003e\n \u003cp\u003e3 (6.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.050541516245488%\" valign=\"top\"\u003e\n \u003cp\u003e0.631\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"47.83393501805054%\" valign=\"top\"\u003e\n \u003cp\u003eCobblestone appearance, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.14801444043321%\" valign=\"top\"\u003e\n \u003cp\u003e4 (10.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.967509025270758%\" valign=\"top\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.050541516245488%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.031*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"47.83393501805054%\" valign=\"top\"\u003e\n \u003cp\u003eNarrow, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.14801444043321%\" valign=\"top\"\u003e\n \u003cp\u003e3 (8.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.967509025270758%\" valign=\"top\"\u003e\n \u003cp\u003e2 (4.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.050541516245488%\" valign=\"top\"\u003e\n \u003cp\u003e0.648\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"47.83393501805054%\" valign=\"top\"\u003e\n \u003cp\u003eDistortion of ileocecal valve, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.14801444043321%\" valign=\"top\"\u003e\n \u003cp\u003e3 (8.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.967509025270758%\" valign=\"top\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.050541516245488%\" valign=\"top\"\u003e\n \u003cp\u003e0.076\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eIBD = Inflammatory bowel disease, * Score of ulceration in lower GI: We divided the lower gastrointestinal (GI) tract into terminal ileum, ileocecal part, ascending colon, transverse colon, descending colon, sigmoid colon and rectum; every part with ulceration meant one score and we accumulated total score.\u0026nbsp;*\u003cem\u003eP\u003c/em\u003e \u0026lt;0.05, ***\u003cem\u003eP\u003c/em\u003e \u0026lt;0.001\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.5 The comparison of histopathological results in patients with colonic ulceration\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe histopathological presentations were including inflammatory cell infiltration, cryptitis, crypt abscess, granulation tissues hyperplasia, and granuloma (Figure 2). We found IBD patients presented more pathological changes, including crypt abscess (\u003cem\u003eP\u003c/em\u003e = 0.013), granulation tissues hyperplasia (\u003cem\u003eP\u003c/em\u003e \u0026lt; 0.001), and granuloma (\u003cem\u003eP\u003c/em\u003e = 0.016), compared to non-IBD patients (Table 5). When comparing Normal IBD, Monogenic IBD-like disorders and non-IBD groups (Table S9), only the characteristic of granulation tissues hyperplasia had statistical differences between children with monogenic IBD-like disorders (3, 42.9%)\u003csub\u003e\u0026nbsp;\u003c/sub\u003eand non-IBD groups (1, 2.1%).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 5 Comparison of\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003ehistopathological\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;results\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;in IBD and non-IBD patients\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"554\"\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.3254972875226%\" rowspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eEvents\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.89150090415913%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eIBD\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(n = 37)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.89150090415913%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eNon-IBD\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(n = 48)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.89150090415913%\" rowspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eP\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"0%\" height=\"36\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"NaN%\" height=\"36\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.3254972875226%\"\u003e\n \u003cp\u003e\u003cstrong\u003eCryptitis, n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.89150090415913%\" valign=\"top\"\u003e\n \u003cp\u003e26 (70.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.89150090415913%\" valign=\"top\"\u003e\n \u003cp\u003e31 (64.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.89150090415913%\" valign=\"top\"\u003e\n \u003cp\u003e0.580\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"0%\" height=\"36\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.3254972875226%\"\u003e\n \u003cp\u003e\u003cstrong\u003eCrypt abscess\u003c/strong\u003e\u003cstrong\u003e, n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.89150090415913%\" valign=\"top\"\u003e\n \u003cp\u003e13 (35.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.89150090415913%\" valign=\"top\"\u003e\n \u003cp\u003e6 (12.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.89150090415913%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.013*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"0%\" height=\"36\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.3254972875226%\"\u003e\n \u003cp\u003e\u003cstrong\u003eGranulation tissues hyperplasia\u003c/strong\u003e\u003cstrong\u003e, n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.89150090415913%\" valign=\"top\"\u003e\n \u003cp\u003e13 (35.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.89150090415913%\" valign=\"top\"\u003e\n \u003cp\u003e1 (2.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.89150090415913%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001***\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"0%\" height=\"36\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.3254972875226%\"\u003e\n \u003cp\u003e\u003cstrong\u003eGranuloma\u003c/strong\u003e\u003cstrong\u003e, n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.89150090415913%\" valign=\"top\"\u003e\n \u003cp\u003e9 (24.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.89150090415913%\" valign=\"top\"\u003e\n \u003cp\u003e2 (4.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.89150090415913%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.016*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"0%\" height=\"36\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eIBD = Inflammatory bowel disease. *\u003cem\u003eP\u003c/em\u003e \u0026lt;0.05, ***\u003cem\u003eP\u003c/em\u003e \u0026lt;0.001\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eWith the development of endoscopic technology, colonic ulcers were found in children with different diagnosis. Due to the particular stage of growth and development in children and different disease spectrum from adults, it is essential to do early differential diagnosis and provide precise treatment. Our study displayed some potential unique indicators for the help of the diagnosis of pediatric IBD differentiating from other disorders with colonic ulcers, though we need larger sample size to confirm the findings. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;In the total of 86 pediatric patients found with ulcers by colonoscopy, the most common diagnosis was IBD. Early-onset IBD patients (\u0026lt;10 years), especially very early-onset IBD (VEO-IBD) patients (\u0026lt;6 years), present a closer relationship with genetic mutations[13]. We defined VEO-IBD patients as monogenic IBD-like disorders when they have a monogenic mutation according to ECCO[7]. In our study, 3 cases were with the mutation of \u003cem\u003eIL10RA\u003c/em\u003e, which was of high frequency in monogenic IBD-like disorders, and the conventional therapy of IBD may have poor efficacy, even with haematopoietic stem cell transplantation\u0026nbsp;[14,15]. Four cases were also with genetic abnormality, including \u003cem\u003eEP300\u003c/em\u003e mutation, \u003cem\u003ePIK3CD\u003c/em\u003e mutation, Wiskott-Aldrich Syndrome, and IPEX syndrome, respectively. These children need early gene detection to confirm the diagnosis for the severe disease progression[16]. Autoimmune diseases had 9 cases, mainly including IgA vasculitis (6/86). IgA vasculitis is one of the most frequent vasculitides in childhood and had similar gastrointestinal manifestations (abdominal pain, hematochezia) with IBD, which needs care for the prognosis\u0026nbsp;[17]. A total of 8 cases of gastrointestinal allergy were found in our study, and the disease occurs frequently in children.\u0026nbsp;Nambu et al. also found the most common diagnoses\u0026nbsp;except for IBD\u0026nbsp;in children who performed colonoscopies, were eosinophilic gastrointestinal disorders, which need food avoidance[18]. Our findings showed that the levels of\u0026nbsp;NLR, ESR, CRP and TNF-\u0026alpha; may distinguish IBD and gastrointestinal allergy.\u0026nbsp;Furthermore, a high proportion of children had intestinal ulcers for infectious enteritis (13/86), which may alert us to strictly control the indications of colonoscopy examination.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eWe mainly focused on comparing IBD with other diseases and the differences may help to increase the differential diagnosis of disease profile. The results displayed that the age of Normal IBD group was mainly \u0026ge; 10 years (60.0%), while the age of children with monogenic IBD-like disorders was mainly \u0026lt; 2 years (85.7%), which was consistent with previous research\u0026nbsp;[19]. Clinical symptoms of children with colonic ulcers, weight loss/failure to thrive, perianal lesions, and oral ulcers had a higher frequency in IBD children than in non-IBD children. These abnormal findings fulfilled the criteria of clinical features in IBD\u0026nbsp;[20,21]. While the age of children was less than 6 years old, clinical characteristics and biochemical indexes lacked significant differences in different diseases. Our findings showed less abdominal pain found in IBD children. The cause indicates that the mild pain was easily neglected due to other serious complaints in this retrospective study. And abdominal pain is a subjective feeling while children may lack correct expression.\u003c/p\u003e\n\u003cp\u003eLaboratory examinations presented lower hemoglobin and albumin expression levels in the IBD group than in the non-IBD group. These were typically elevated in active disease while mild IBD could show normal results in routine blood tests\u0026nbsp;[21]. Sabery et al. found anemia as a predictor for IBD was 83% sensitivity, and albumin is also a sensitive maker when combined with inflammatory indexes like CRP or ESR\u0026nbsp;[8,9]. The Intestinal ulcer lesions may contribute to the condition that IBD children are more susceptible to anemia than other diseases. Platelet aggregation at the colonic mucosae was common in colitis and IBD[22], and our findings of the level of platelet and D-Dimer is higher in IBD children, indicating the IBD children had an increased risk for thrombus development than children with other colitis. As a marker of reflecting systemic inflammation, NLR has been found to be significantly increased at diagnosis and active disease of IBD children compared with healthy subjects[23-25]. Our results further found that NLR was also considerably higher in IBD group than in non-IBD group, even though all patients had colonic ulceration.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe expression levels of ESR and CRP were still significantly higher in IBD group. These markers may also be relatively sensitive and specific to distinguish IBD from other diseases in children with ulcers in colon. Besides, FCP is a kind of protein from neutrophils, considered as a noninvasive and valuable marker of intestinal inflammation[26,27]. We found that the expression levels of FCP between two groups did not show statistical differences (\u003cem\u003eP\u003c/em\u003e = 0.065). FCP in both IBD (78.6%) and non-IBD patients (58.3%) was mainly \u0026gt; 1500 ug/g. The reason indicates that young children have a higher baseline value of FCP compared with normal adults[27]. In addition, the research object in our study were all children with colonic ulceration, whose intestinal inflammation was relatively severe. Herein, FCP may not be sensitive to distinguishing IBD among children with colonic ulcerations.\u003c/p\u003e\n\u003cp\u003eOtherwise, IgG\u0026nbsp;was also at higher levels in IBD group. IBD is a disorder closely related to immune reaction. IgG was predicted to be associated with IBD severity and response to gut microbiota\u0026nbsp;[28]. Pro-inflammatory factors including IL-1\u0026beta;, and TNF-\u0026alpha;, were increasing the expression level in IBD group. The finding indicates that IL-1\u0026beta; may be a potential specific marker of IBD in pediatric patients. The upstream mechanisms and signal pathways of\u0026nbsp;IL-1\u0026beta;\u0026nbsp;may be interesting perspectives of pathogeny which identify IBD from colonic ulcerative diseases, like mediating NLRP3 activation which regulates the generation and maturation of IL-1\u0026beta;\u0026nbsp;[29-31]. In addition, anti-TNF-\u0026alpha; drugs have been widely used in treating children with IBD[32]. Anti- IL-1\u0026beta; may also be an effective therapeutic target in IBD patients in the future.\u003c/p\u003e\n\u003cp\u003eColonoscopy revealed statistical differences in ulcer distribution between IBD and non-IBD groups. The discrepancy in ulcer distribution range may help to distinguish colonic ulceration, especially between CD and infectious enteritis. Otherwise, cobblestone appearance was only found in IBD group, which fulfilled the criteria of endoscopic characteristics in CD[20]. Histopathological results play essential roles in the different diagnoses of intestinal disorders [21]. The characteristics of mucosal tissue with hematoxylin \u0026amp; eosin staining included cryptitis, crypt abscess, granulation tissues hyperplasia, granuloma, lymphocyte proliferation, and eosinophil infiltration. The histological phenotype is hardly distinguished for the overlapping in morphological aspects between IBD and non-IBD patients[10]. In children with colonic ulcers, we found the significant differences in the change of crypt abscess, granulation tissues hyperplasia, and granuloma between IBD and non-IBD groups. Granuloma is a kind of local change of chronic inflammation, which could be observed typically in CD [21]. Characteristic pathological changes still need further exploration in other intestinal disorders.\u0026nbsp;\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn conclusion, the etiologies caused by colonic ulcers are complex and diverse, and primary diseases are IBD, infectious enteritis, autoimmune diseases, and gastrointestinal allergy. Hemoglobin, albumin, platelet, NLR, ESR, CRP, IgG, IL-1\u0026beta;, IL-6, and TNF-\u0026alpha; could be considered as essential reference indicators for IBD in children with colonic ulcers. The sensitivity and specificity still need a large sample size to verify these indexes. The different changes found in colonoscopy in the study are hoped to help further understand intestinal diseases and improve the diagnosis in children with colonic ulcers.\u003c/p\u003e\n"},{"header":"Abbreviations","content":"\u003cp\u003eCD: Crohn\u0026apos;s disease\u003c/p\u003e\n\u003cp\u003eCRP: C-reactive proteinA\u003c/p\u003e\n\u003cp\u003eECCO: European Crohn\u0026apos;s and Colitis Organisation\u003c/p\u003e\n\u003cp\u003eESR: erythrocyte sedimentation rate\u003c/p\u003e\n\u003cp\u003eFCP: fecal calprotectin\u003c/p\u003e\n\u003cp\u003eFPIES: food protein-induced enterocolitis\u003c/p\u003e\n\u003cp\u003eIBD: Inflammatory bowel disease\u003c/p\u003e\n\u003cp\u003eIgG: Immunoglobulin G\u003c/p\u003e\n\u003cp\u003eIL-1\u0026beta;: Interleukin-1\u0026beta;\u003c/p\u003e\n\u003cp\u003eIPEX syndrome: immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome\u003c/p\u003e\n\u003cp\u003eIQR: interquartile range\u003c/p\u003e\n\u003cp\u003eLCH: Langerhans cell histiocytosis\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eNEC: neonatal necrotizing enterocolitis\u003c/p\u003e\n\u003cp\u003eNLR: neutrophil-to-lymphocyte ratio\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSLE: systemic lupus erythematosus\u003c/p\u003e\n\u003cp\u003eUC: Ulcerative colitis\u003c/p\u003e\n\u003cp\u003eVEO-IBD: very early-onset IBD\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eConflict of interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors have no conflicts of interest to disclose.\u003c/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eConsent to participate declaration\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent was obtained from the parents of all individual participants included in the study.\u003c/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was supported by National Natural Science Foundation of China (81701486), and Foundation of Science and Technology Commission of Shanghai Municipality (16ZR1428400).\u003c/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eW. Y. and Y. W. developed the study design. Y. Y. and\u0026nbsp;Y. T. collected the data and wrote the manuscript.\u0026nbsp;Y. X., Y. C., H. F., and Q. W. analyzed the data.\u0026nbsp;W. Y. and Y. W. also reviewed and modified the manuscript. All of the authors approved the manuscript to be published.\u0026nbsp;\u003c/p\u003e\n\n"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eEdden Y, Shih SS, Wexner SD (2009) Solitary rectal ulcer syndrome and stercoral ulcers. Gastroenterol Clin North Am 38:541-545\u003c/li\u003e\n\u003cli\u003eCai J, Li F, Zhou W, Luo HS (2007) Ileocecal ulcer in central China: case series. Dig Dis Sci 52:3169-3173\u003c/li\u003e\n\u003cli\u003eLee YJ, Yang SK, Byeon JS, Myung SJ, Chang HS, Hong SS, Kim KJ, Lee GH, Jung HY, Hong WS, Kim JH, Min YI, Chang SJ, Yu CS (2006) Analysis of colonoscopic findings in the differential diagnosis between intestinal tuberculosis and Crohn\u0026apos;s disease. 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BMC Gastroenterol 19:149\u003c/li\u003e\n\u003cli\u003eKuenzig ME, Fung SG, Marderfeld L, Mak JWY, Kaplan GG, Ng SC, Wilson DC, Cameron F, Henderson P, Kotze PG, Bhatti J, Fang V, Gerber S, Guay E, Kotteduwa Jayawarden S, Kadota L, Maldonado DF, Osei JA, Sandarage R, Stanton A, Wan M, Benchimol EI (2022) Twenty-first Century Trends in the Global Epidemiology of Pediatric-Onset Inflammatory Bowel Disease: Systematic Review. Gastroenterology 162:1147-1159.e1144\u003c/li\u003e\n\u003cli\u003eOliveira SB, Monteiro IM (2017) Diagnosis and management of inflammatory bowel disease in children. Bmj 357:j2083\u003c/li\u003e\n\u003cli\u003eLevine A, Koletzko S, Turner D, Escher JC, Cucchiara S, de Ridder L, Kolho KL, Veres G, Russell RK, Paerregaard A, Buderus S, Greer ML, Dias JA, Veereman-Wauters G, Lionetti P, Sladek M, Martin de Carpi J, Staiano A, Ruemmele FM, Wilson DC (2014) ESPGHAN revised porto criteria for the diagnosis of inflammatory bowel disease in children and adolescents. 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Int Immunopharmacol 101:108235\u003c/li\u003e\n\u003cli\u003eZahmatkesh A, Sohouli MH, Hosseini SME, Rohani P (2023) The role of platelet-to-lymphocyte ratio and neutrophil-to-lymphocyte ratio in the diagnosis and severity of inflammatory bowel disease in children. Eur J Pediatr 182:4263-4270\u003c/li\u003e\n\u003cli\u003eRicciuto A, Griffiths AM (2019) Clinical value of fecal calprotectin. Crit Rev Clin Lab Sci 56:307-320\u003c/li\u003e\n\u003cli\u003eLężyk-Ciemniak E, Tworkiewicz M, Wilczyńska D, Szaflarska-Popławska A, Krogulska A (2021) Usefulness of Testing for Fecal Calprotectin in Pediatric Gastroenterology Clinical Practice. Med Princ Pract 30:311-319\u003c/li\u003e\n\u003cli\u003eRengarajan S, Vivio EE, Parkes M, Peterson DA, Roberson EDO, Newberry RD, Ciorba MA, Hsieh CS (2020) Dynamic immunoglobulin responses to gut bacteria during inflammatory bowel disease. Gut Microbes 11:405-420\u003c/li\u003e\n\u003cli\u003eAschenbrenner D, Quaranta M, Banerjee S, Ilott N, Jansen J, Steere B, Chen YH, Ho S, Cox K, Arancibia-C\u0026aacute;rcamo CV, Coles M, Gaffney E, Travis SP, Denson L, Kugathasan S, Schmitz J, Powrie F, Sansom SN, Uhlig HH (2021) Deconvolution of monocyte responses in inflammatory bowel disease reveals an IL-1 cytokine network that regulates IL-23 in genetic and acquired IL-10 resistance. Gut 70:1023-1036\u003c/li\u003e\n\u003cli\u003eBauer C, Duewell P, Mayer C, Lehr HA, Fitzgerald KA, Dauer M, Tschopp J, Endres S, Latz E, Schnurr M (2010) Colitis induced in mice with dextran sulfate sodium (DSS) is mediated by the NLRP3 inflammasome. Gut 59:1192-1199\u003c/li\u003e\n\u003cli\u003eMan SM (2018) Inflammasomes in the gastrointestinal tract: infection, cancer and gut microbiota homeostasis. Nat Rev Gastroenterol Hepatol 15:721-737\u003c/li\u003e\n\u003cli\u003ePeyrin-Biroulet L, Deltenre P, de Suray N, Branche J, Sandborn WJ, Colombel JF (2008) Efficacy and safety of tumor necrosis factor antagonists in Crohn\u0026apos;s disease: meta-analysis of placebo-controlled trials. Clin Gastroenterol Hepatol 6:644-653\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bped","sideBox":"Learn more about [BMC Pediatrics](http://bmcpediatr.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bped/default.aspx","title":"BMC Pediatrics","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Colonoscopy, Ulcer, Colon, Diagnosis, Inflammatory bowel disease","lastPublishedDoi":"10.21203/rs.3.rs-4603636/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4603636/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eA wide variety of diseases mimic inflammatory bowel disease (IBD). This study aimed to reduce the misdiagnosis among children with colonic ulcers, unfolding the pediatric disease profiles.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eEighty-six pediatric patients with colonic ulcers detected by colonoscopy were enrolled in the retrospective study. Children were divided into different groups according to the final diagnosis. The clinical characteristics, laboratory examinations and histopathological results were compared between the groups.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eIBD (n\u0026thinsp;=\u0026thinsp;37) was just responsible for 43% of patients with colonic ulceration. Other diagnosis mainly included autoimmune diseases (n\u0026thinsp;=\u0026thinsp;9), infectious enteritis (n\u0026thinsp;=\u0026thinsp;13), gastrointestinal allergy (n\u0026thinsp;=\u0026thinsp;8), and other diseases (n\u0026thinsp;=\u0026thinsp;19). Comparing IBD and non-IBD groups, children with IBD had a higher frequency of symptoms like weight loss/failure to thrive (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), perianal lesions (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.001), and oral ulcers (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.022), and higher expression levels of platelet (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.006), neutrophil-to-lymphocyte (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.001), erythrocyte sedimentation rate (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), C-reactive protein (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), Immunoglobulin G (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.012), Interleukin-1β (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.003), IL-6 (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.024) and TNF-α (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.026). Otherwise, expression levels of hemoglobin (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and albumin (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.001) were lower in IBD patients. Besides, a wider ulcer range distribution in the lower gastrointestinal tract was found in the IBD group (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eWe displayed potential indicators (like platelet, neutrophil-to-lymphocyte ratio and ulcer distribution character) to help diagnose pediatric IBD with colonic ulcers differentiating from other disorders more prudent.\u003c/p\u003e","manuscriptTitle":"Clinical Analysis and Identification of Pediatric Patients with Colonic Ulceration","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-07-18 20:03:47","doi":"10.21203/rs.3.rs-4603636/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-07-19T05:59:17+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-07-17T06:58:39+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-07-08T15:39:24+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"161476340182089552284065416374135823545","date":"2024-07-01T12:51:05+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"147347962748472025107959572182644427766","date":"2024-06-30T08:17:45+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-06-28T13:41:40+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2024-06-26T09:06:18+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-06-20T14:56:27+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-06-20T14:54:31+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Pediatrics","date":"2024-06-19T06:24:24+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bped","sideBox":"Learn more about [BMC Pediatrics](http://bmcpediatr.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bped/default.aspx","title":"BMC Pediatrics","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"83f59755-30ff-4828-af21-7c08e3292ce8","owner":[],"postedDate":"July 18th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-11-04T16:24:17+00:00","versionOfRecord":{"articleIdentity":"rs-4603636","link":"https://doi.org/10.1186/s12887-024-05174-3","journal":{"identity":"bmc-pediatrics","isVorOnly":false,"title":"BMC Pediatrics"},"publishedOn":"2024-11-01 15:57:22","publishedOnDateReadable":"November 1st, 2024"},"versionCreatedAt":"2024-07-18 20:03:47","video":"","vorDoi":"10.1186/s12887-024-05174-3","vorDoiUrl":"https://doi.org/10.1186/s12887-024-05174-3","workflowStages":[]},"version":"v1","identity":"rs-4603636","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4603636","identity":"rs-4603636","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}