Lymphonodular Hyperplasia Research Articles

Diagnostic Utility of Mucosal Biopsies Taken During Colonoscopy-Guided Colonic Manometry Catheter Placement.

The diagnostic utility of mucosal biopsies taken during colonoscopy-guided colonic manometry catheter placement is unknown. The aims of our study were to determine the frequency and histopathology results of mucosal biopsies during these procedures and to assess whether there were any associations between the histology or gross findings with manometry results. We performed a retrospective chart review of children who had a colonic manometry study completed between 2008 and 2020 at a quaternary children's hospital. We captured patient demographics, biopsy locations, histopathology results, gross endoscopy findings, and manometry results. The chi-squared test and when appropriate Fisher exact test was used to evaluate categorical associations. One hundred forty-eight patients were included. One hundred eighteen (80%) had colonic biopsy and 63 (43%) had ileal biopsy. Colonic histology findings, which patients could have multiple, included lymphonodular hyperplasia (34%), normal (27%), chronic inflammation (24%), melanosis coli (21%), colonic eosinophilia (10%), and acute inflammation (8%). Ileal histology findings included increased Peyer patches (44%), normal (44%), acute inflammation (11%), chronic inflammation (3%), eosinophilia (5%), and eosinophilic ileitis (3%). The majority of acute and chronic inflammation was graded as mild. There were no statistically significant associations of histology to gross endoscopy or manometry findings. Colonic biopsies are obtained in the majority of patients presenting for colonic manometry evaluation with ileal biopsies obtained less frequently. Histopathology findings are noted frequently, but the majority are the result of or did not impact clinical care. There were no associations between abnormal histopathology or abnormal gross endoscopy findings with colonic manometry results.

Disease patterns among Saudi children undergoing colonoscopy for lower gastrointestinal bleeding: Single tertiary care center experience.

: The yield of colonoscopy in cases presenting with lower gastrointestinal bleeding (LGIB) in previously published studies varies according to several factors, including endoscopic skills, histopathological experience, and pattern of colonic pathology in different countries. The local literature is limited to a single small 20-year-old study. Our objective was to provide updated data on the diagnostic yield of colonoscopy in Saudi children with LGIB in Saudi Arabia. : This was a retrospective analysis of pediatric patients (0-14 years of age) who underwent colonoscopy for LGIB at the King Fahad Medical City (KFMC), from 2008 to 2018. LGIB was defined as fresh or dark blood per rectum. : During the study period, 175 children underwent colonoscopy for LGIB (99 males, mean age 7.05 ± 3.81 years), which constituted 53.5% of indications for colonoscopy procedures (n = 327) in our center. The terminal ileum was intubated in 81% of the procedures. Overall, inflammatory bowel disease (IBD) was the most commonly identified cause of LGIB (32% ) followed by colonic lymphonodular hyperplasia (CLNH) in 17% and juvenile polyp and rectal mucosal prolapse syndrome (RMPS), 11% each. On sub-analysis, cow's milk protein allergy (CMPA) and CLNH were the most common causes in infants and toddlers, 35% each; IBD (26.5%) and polyps (22.4%) in young children (2-6 years), and IBD (36%), CLNH (14.9%) and RMPS (14%) in older children (6-14 years). In comparing the IBD to the non-IBD group, IBD patients were older (mean 8.37 vs. 6.46 years, P = 0.002) and more likely to have diarrhea, weight loss, high erythrocyte sedimentation rate, anemia, and hypoalbuminemia (odds ratio 24, 11, 10.7, 6.5, and 4, respectively). Colonoscopy had a sensitivity of 97%, specificity of 100%, positive predictive value of 100%, negative predictive value of 81.4%, and accuracy of 97% in diagnosing LGIB. : Colonoscopy is an effective diagnostic tool in children with LGIB with a high diagnostic yield. Besides IBD, CLNH and RMPS are two other important pathologic entities that need to be considered in a child with LGIB.

Ileocolonic Lymphonodular Hyperplasia in Children Related to Etiologies Ranging from Food Hypersensitivity to Familial Mediterranean Fever

Objective: We aimed to share our observations on the demographics, clinical characteristics, and outcomes of lymphonodular hyperplasia (LNH) in children. Subjects and Methods: The study included children on whom colonoscopy was performed between January 2015 and May 2018 (n = 361). Demographics, treatment modalities, and outcomes of the patients with LNH were recorded. Results: LNH was found in 66 patients (18.3%; mean age 8.6 ± 5.96 years, 59.1% male). We found that the etiologic factors were food hypersensitivity (FH) in 25 (37.8%), nonspecific colitis in 12 (18.2%), irritable bowel syndrome in 10 (15.2%), familial Mediter­ranean fever in 7 (10.6%), primary immunodeficiency in 4 (6.1%), and intestinal dysmotility, oxyuriasis, Crohn’s disease, and giardiasis in 1 (1.5%) patient. Additionally, in the genetic analysis of patients with idiopathic LNH (n = 4), we detected heterozygote MEFV mutations in all. Cow’s milk and egg (25%) were the most common allergens in patients with FH. Symptoms of all patients (n = 25) improved after an elimination diet. Conclusions: LNH is a common finding in pediatric colonoscopies with a variety of etiologies ranging from FH and familial Mediterranean fever to immunodeficiency.

3073 Eosinophilic Gastroenteritis and Eosinophilic Proctocolitis With a Large Rectal Sessile Serrated Adenoma: A Rare Association

INTRODUCTION: Eosinophilic Gastrointestinal Disorders (EGID) are a group of rare disorders characterized by eosinophilic infiltration of the gastrointestinal tract. Eosinophilic gastroenteritis (EGE), eosinophilic colitis (EC) and eosinophilic proctitis (EP) are different types of EGID. We report a case of rare association of EGID and a large sessile serrated adenoma in a middle-aged Hispanic female. CASE DESCRIPTION/METHODS: A 49-year-old Hispanic female presented with epigastric discomfort, nausea and hematochezia. The symptoms were insidious in onset and evolved over the span of 3 years. Upper GI Endoscopy showed mild diffuse erythematous mucosa in the antrum and body of the stomach. Colonoscopy showed a few superficial ulcers in the terminal ileum, two polyps in the transverse colon and a large laterally spreading polypoid lesion in the rectum with adjacent multiple small polypoid lesions (Figures 1 and 2). Histological assessment of the gastric biopsy specimen revealed chronic active gastritis, numerous H. pylori, in addition to very high number of eosinophils in the lamina propria. Biopsies of ileum, colon and the rectum also revealed very high number of eosinophils in the lamina propria. Stool for ova and parasite examinations were negative and no peripheral eosinophilia was noted. Patient did not have any food or environmental allergies. Other disorders that could contribute to eosinophil infiltration of the GI tract were ruled out. Hematochezia was likely due to eosinophilic proctitis and rectal polypoid lesion. Although exact eosinophilic count in the biopsy specimen of the stomach, small bowel and the colon was not reported, the clinical presentation and histology was likely consistent with EGID. Patient was treated for H. Pylori infection. Endoscopic submucosal dissection of the rectal polypoid lesion was performed (Figure 3). Pathology revealed sessile serrated adenoma. DISCUSSION: Eosinophilic gastrointestinal disorders are a group of rare gastrointestinal diseases with non-specific symptoms and clinical presentation. Diagnosis of EGE, EC and EP involves evaluating for presence of gastrointestinal symptoms, histopathology finding of eosinophilic infiltration of the GI tract and ruling out secondary causes of eosinophilia. Endoscopic examination may reveal patchy erythema, loss of vascularity and lymphonodular hyperplasia mostly localized to the rectum. The authors report this rare case of possible association of EGID and sessile serrated adenoma.

Short article: The endoscopic and histologic findings of infants who have experienced brief resolved unexplained events.

A brief resolved unexplained event (BRUE) describes an event associated with a change in muscle tone, color, respiration, and responsiveness that is unexplained after an appropriate examination. Some infants with higher risk BRUE may undergo endoscopy as part of their evaluation. This retrospective study aimed to identify the endoscopic findings in infants who have experienced a higher risk BRUE. We also compared the characteristics, prenatal, natal, and postnatal risk factors between 23 infants who underwent endoscopic evaluation and 23 race-matched/sex-matched/term-matched/preterm-matched infants who did not undergo endoscopic evaluation. This was a retrospective descriptive study. Infants were identified from a query of medical records using the ICD-10 code for BRUE (R68.13). Of 119 infants with BRUE, 23 infants with higher risk BRUE underwent an esophagogastroduodenoscopy and flexible sigmoidoscopy. Apnea (87%) was the most common presentation of BRUE. Most were female (57%) with a mean age at BRUE presentation of 2.73 months. We found 10 (43.5%) term infants and 13 (56.5%) preterm infants in our study. There were no significant differences in characteristics, prenatal, natal, and postnatal risk factors between the infants who underwent endoscopy and those who did not undergo endoscopy. The most common abnormal endoscopic finding was lymphonodular hyperplasia (LNH) associated with eosinophilia in the rectosigmoid colon. The proportion of females in the LNH group was significantly higher than the non-LNH group. Rectosigmoid LNH and eosinophilia, which are associated with milk soy protein intolerance (MSPI), were the most common findings on endoscopic evaluation. Although there is no proof of causation between MSPI and BRUE, MSPI should be considered in the differential diagnosis for higher risk BRUE.

DOP010 Activating PIK3CD mutations cause severe intestinal lymphonodular hyperplasia and an IBD-like phenotype

DOP010 Activating PIK3CD mutations cause severe intestinal lymphonodular hyperplasia and an IBD-like phenotype

Iron Requirements for Infants with Cow Milk Protein Allergy

H istorically, cow milk has been used as a major source of protein and balanced nutrition for infants and children in resource-rich and resource-constrained countries. It is a rich source of energy, protein, and calcium. It is also an important source of fat; many of its fatty acids are readily metabolized to essential omega-3 fatty acids. Regular consumption of milk during childhood has been shown to enhance bone density later in life. However, reliance upon whole pasteurized cow milk as the sole or major source of nutrition for infants during the first year of life can increase the risk for iron deficiency and, in extreme cases, iron-deficient anemia (IDA) for a number of reasons. In 1972, Woodruff et al showed that 7 of 12 infants (ages 7-17 months) with IDA who ingested between 720 and 1920 mL whole milk daily had higher albumin turnover rates than a group of 5 normal infants. Parenteral iron had no effect on albumin turnover, but replacing whole milk with reconstituted evaporated milk or soy formula decreased the high albumin turnover rates to normal levels, suggesting that large amounts of cow milk protein could result in iron and protein loss in the gastrointestinal tract. Cow milk contains low levels of ascorbic acid, a factor that increases iron absorption, and certain proteins that negatively impact iron absorption. Cow milk contains about 4 times more calcium than human milk, and calcium negatively impacts iron absorption. Furthermore, cow milk has a higher protein concentration than human milk, and ingestion of large amounts can lead to metabolic and fluid imbalances, particularly in children with febrile illnesses. Thus, several entities have recommended against whole cow milk ingestion until 9-12 months and then, only when given in moderate amounts in conjunction with appropriate complementary foods.

Gastrointestinal hemorrhage in a 21-month-old girl in the course of lymphonodular hyperplasia (LNH). Case report

Gastrointestinal hemorrhage in a 21-month-old girl in the course of lymphonodular hyperplasia (LNH). Case report

Intussusception Associated With Adenovirus

A 7-month-old girl presented with irritability, bilious vomiting, and hematochezia. A week before presentation she had an upper respiratory tract infection. Initial evaluation showed distended bowel loops on abdominal film and intussusception of the ascending colon on ultrasound. While attempting a reduction with an air contrast enema, an air leak occurred, necessitating an ileocecal resection and reanastomosis. Gross examination of the specimen showed a partially necrotic segment of terminal ileum invaginated into the cecum. Mucosal thickening and lymphonodular hyperplasia in the ileocecal valve was consistent with a lead point (Fig. 1). Histological examination showed active epithelial injury with ulcerations, granulation, and necrosis. Surface epithelium contained transformed cells with smudgy, enlarged nuclei consistent with Cowdry type B viral inclusions (Fig. 2). The presence of adenovirus was confirmed by immunohistochemistry (Fig. 3).FIGURE 1: Ileocecum showing mural edema (arrows) and focal hemorrhagic necrosis.FIGURE 2: High-power view showing homogeneous eosinophilic intranuclear inclusions (arrows) (H&E, original magnification ×40).FIGURE 3: Immunohistochemistry utilizing an Adenovirus antibody confirms the presence of the virus (IHC, DAB chromogen, hematoxilin counterstain, original magnification ×10).Intussusception is the most common cause of intestinal obstruction in children younger than 2 years. Ninety percent of the cases are associated with hyperplastic lymphoid tissue, suggesting an infectious cause. Studies conducted in the United States have identified species C adenoviruses in fewer than 15% of intussusception cases (1). In a small Mexican series species C was also demonstrated in all patients with adenovirus infection (2).

Characteristics of allergic colitis in breast-fed infants in the absence of cow’s milk allergy

To investigate the characteristics of mucosal lesions and their relation to laboratory data and long-term follow up in breast-fed infants with allergic colitis. In this study 31 breast-fed infants were prospectively evaluated (mean age, 17.4 wk) whose rectal bleeding had not ceased after a maternal elimination diet for cow's milk. Thirty-four age-matched and breast-fed infants (mean age, 16.9 wk) with no rectal bleeding were enrolled for laboratory testing as controls. Laboratory findings, colonoscopic and histological characteristics were prospectively evaluated in infants with rectal bleeding. Long-term follow-up with different nutritional regimes (L-amino-acid based formula or breastfeeding) was also included. Iron deficiency, peripheral eosinophilia and thrombocytosis were significantly higher in patients with allergic colitis in comparison to controls (8.4 ± 3.2 μmol/L vs 13.7 ± 4.7 μmol/L, P < 0.001; 0.67 ± 0.49 G/L vs 0.33 ± 0.17 G/L, P < 0.001; 474 ± 123 G/L vs 376 ± 89 G/L, P < 0.001, respectively). At colonoscopy, lymphonodular hyperplasia or aphthous ulceration were present in 83% of patients. Twenty-two patients were given L-amino acid-based formula and 8 continued the previous feeding. Time to cessation of rectal bleeding was shorter in the special formula feeding group (mean, 1.4 wk; range, 0.5-3 wk) when compared with the breast-feeding group (mean, 5.3 wk; range, 2-9 wk). Nevertheless, none of the patients exhibited rectal bleeding at the 3-mo visit irrespective of the type of feeding. Peripheral eosinophilia and cessation of rectal bleeding after administration of elemental formula correlated with a higher density of mucosal eosinophils. Infant hematochezia, after cow's milk allergy exclusion, is generally a benign and probably self-limiting disorder despite marked mucosal abnormality. Formula feeding results in shorter time to cessation of rectal bleeding; however, breast-feeding should not be discouraged in long-lasting hematochezia.

705 Gastrointestinal Hemorrhage in a 21-Month-Old Girl in The Course of Lymphoodular Hyperplasia. Case Report

Gastrointestinal hemorrage is an emergency condition requiring immediate diagnostics. Lymphonodular hyperplasia, as a cause of bleeding from the gastrointestinal tract in children, is a rarely observed pathology of unknown etiology....

Serum and Tissue CD23, IL‐15, and FasL in Cow's‐Milk Protein–sensitive Enteropathy and in Coeliac Disease

The aim of the study was to explore pathogenesis and find new serum markers for cow's-milk-sensitive enteropathy (CMSE) and coeliac disease (CD). We assessed the intestinal expression and serum concentration of CD23, IL-15, and FasL. We hypothesised that the serum levels of CD23, a protein expressed in the lymphoid follicles, would be associated with lymphonodular hyperplasia (LNH), a feature characteristic of CMSE. We also presumed that interleukin (IL)-15 and FasL, functionally connected with proliferation and apoptosis of the intraepithelial lymphocytes (IELs), would relate with the increased numbers of IELs present in both CMSE and CD. Twenty-three children with CMSE, 20 with untreated CD, and 14 controls were studied for CD3, α/β- and γ/δ-expressing IELs, and for duodenal and ileal expression of CD23, FasL, and IL-15 by immunohistochemistry, and for serum concentration of sCD23, sFasL, and sIL-15 by enzyme-linked immunosorbent assay. There was a trend for increase in sCD23 serum levels in untreated CMSE and in CD (P = 0.074; P = 0.077). CD23 was expressed in the mucosal germinal centres, but sCD23 was not related to presence of LNH. In CMSE, there was a trend for increase in serum sFasL (P = 0.07) and high levels associated with LNH (P = 0.025) and correlated with the IEL numbers (P < 0.05). Mucosal high endothelial venules adjacent to lymphoid follicles showed an intensive FasL expression. Serum sCD23 shows a trend of increment in CMSE and CD, and in the latter, sCD23 level may provide information about the severity of villous atrophy. In CMSE, high serum sFasL indicates both LNH and an increase of IELs, suggesting importance of FasL-mediated mechanisms in the pathogenesis of these features characteristic of CMSE. Further studies are necessary to evaluate whether intensive FasL expression in mucosal high endothelial venules presents a regulatory element in mucosal immunity.

B Cell Infiltration and Lymphonodular Hyperplasia in Bladder Submucosa of Patients With Persistent Bacteriuria and Recurrent Urinary Tract Infections

We defined chronic inflammatory cell types in bladder submucosa and the presence of umbrella cells on the surface of bladder epithelium in patients 5 to 21 years old with persistent bacteriuria due to neurogenic bladder and recurrent urinary tract infections associated with vesicoureteral reflux. Bladder mucosa biopsies from 12 patients and 6 controls were fixed in Carnoy's solution and examined for T cells (CD3, CD4, CD8), B cells (CD79) and plasma cells (CD138). The number of cells in a defined area of submucosa was determined by counting all nuclei in the area. A contiguous section was also stained for uroplakin expression with a monoclonal antibody against uroplakin III to ascertain the integrity of bladder umbrella cells. B cells, plasma cells and lymphoid nodules were found only in patient biopsies. T cell expression was evident in patient and control biopsies. Uroplakin staining of surface epithelium was uniform from control biopsies but spotty or entirely absent from patient biopsies. Patients with persistent bacteriuria or recurrent urinary tract infections had significant B cell infiltration in the submucosa, including lymphoid nodules. These inflammatory changes are likely due to antigenic stimulation from repeated exposure to bacteria. These changes are associated with frequent absence of uroplakin on surface epithelium.

Abnormal Gastrointestinal Histopathology in Children With Autism Spectrum Disorders.

OBJECTIVES:: The significance of the association between many gastrointestinal (GI) pathologies and autism has yet to be discovered. The aim of the present study was to review available evidence documenting any link between autism and GI histopathology in children. MATERIALS AND METHODS:: In a systematic review, the following sources were searched: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (1980-August week 2, 2009), EMBASE (1980-August week 2, 2009), PubMed (last 180 days), Web of Science, and Scopus, using the terms "autism" or "autistic spectrum disorder" and "intestinal" or "gastrointestinal" or "colitis." In addition, relevant studies were identified through browsing the reference lists of the included articles for relevant citations. All children younger than 18 years old with autistic spectrum disorder who were examined for abnormal GI histopathology were included. Cohort studies published in the English language, reporting GI histopathological examination findings in children with autism, were included. Two independent authors performed data extraction. The methodological quality of each trial was assessed. RESULTS:: Eight studies have reported the histopathological features of the GI tract in children with autism and fulfilled inclusion criteria. In general, none of these trials appeared to be of high quality. Apart from intestinal lymphonodular hyperplasia, the majority of these findings were not consistent. CONCLUSIONS:: GI pathological findings in children with autism have been inconsistent. The present available evidence does not support or refute a link between GI histopathology and autism in children. The significance of intestinal lymphonodular hyperplasia in these children is unknown. Large properly designed prospective controlled trials addressing this issue are required.

The feasibility of wireless capsule endoscopy in detecting small intestinal pathology in children under the age of 8 years: a multicentre European study

Objective:To systematically evaluate the feasibility and methodology to carry out wireless capsule endoscopy (WCE) in children <8 years to define small intestinal pathology.Design:Prospective European multicentre study with negative prior investigation.Patients...

The Clinical and Histopathologic Findings of Lymphonodular Hyperplasia of the Colon in Infancy and Childhood

The Clinical and Histopathologic Findings of Lymphonodular Hyperplasia of the Colon in Infancy and Childhood

Food Hypersensitivity as a Cause of Rectal Bleeding in Adults

Rectal bleeding and lymphonodular hyperplasia (LNH) in children can be caused by food hypersensitivity (FH). Our aim was to verify whether similar clinical and endoscopy presentations in adults can be due to FH. Consecutive adult patients with rectal bleeding were enrolled. All underwent routine assays, colonoscopy, and histology study. Ten of 64 (15%) patients showed LNH as the unique sign at colonoscopy. An oligoantigenic diet resolved the rectal bleeding in 9 patients, and the reintroduction of several foods caused symptom reappearance. Double-blind placebo-controlled challenges with cow's milk and wheat protein confirmed the FH; symptoms reappeared 1-96 hours after the challenge. None of the patients were positive for IgE-mediated assays. In patients with LNH and FH, histology of the ileum and colon mucosa showed a higher number of lymphoid follicles and intraepithelial and lamina propria eosinophils compared with the other patients with rectal bleeding. Recurrent rectal bleeding can be caused by FH in adult patients. Endoscopic evidence of LNH characterizes these cases.

No association between lymphonodular hyperplasia and CARD15 mutations

No association between lymphonodular hyperplasia and CARD15 mutations

Ileal Lymphonular Hyperplasia Is Not Associated With NOD2/CARD15 Mutations

Lymphonodular hyperplasia (LNH) is a mass of lymphoid tissue that has been described in the terminal ileum, colon and duodenum mainly in children. Controversy exists regarding the benign nature of LNH. The combination of chronic abdominal pain and hematochezia leads many of these patients to undergo investigations for inflammatory bowel diseases. NOD2/CARD15 on chromosome 16 has been identified as a susceptibility gene for Crohn disease (CD). No study has yet examined the possible association of NOD2/CARD15 mutations with patients with LNH. The purpose of this study was to investigate the presence of NOD2/CARD15 mutations in patients with clinically proven LNH. Children and young adults with gastrointestinal symptoms diagnosed as having terminal ileum LNH were eligible for the study. The study group consisted of 32 patients (15 males and 17 females), age range 3-23 years, mean 13.1 +/- 5 years. Twenty-seven (84%) had abdominal pain, 3 (9%) had rectal bleeding. The duration of symptoms ranged from 1-60 months (17.9 +/- 14.5). Only 2 patients (6.2%) were found to be heterozygote for the NOD2/CARD15 mutation (1007 fs), whereas all of the others did not carry any of the 3 common mutant alleles. This number is significantly lower (P < 0.001) than the mutation prevalence demonstrated in both pediatric and adult Israeli CD patients. NOD2/CARD15 mutations are not associated with LNH. This may strengthen the lack of association between CD and LNH that has been previously reported. We suggest that genotyping NOD2/CARD15 may help to distinguish LNH from inflammatory bowel diseases in selected patients.

Common Variable Immunodeficiency Presenting as Lymphonodular Hyperplasia, Pernicious Anemia and Breast Cancer

Common Variable Immunodeficiency Presenting as Lymphonodular Hyperplasia, Pernicious Anemia and Breast Cancer