Clinicopathological significance of lymphocytic colitis/collagenous colitis in inflammatory bowel disease.

Patients with inflammatory bowel disease (IBD) may occasionally present with lymphocytic colitis/collagenous colitis (LC/CC) either before or after the onset of IBD. Although a few reports have described a small number of such cases, the relationship between these 2 disorders is still unclear. We evaluated 27 patients with diagnosis of either ulcerative colitis (UC) or Crohn disease (CD) and LC/CC. Clinical, endoscopic, and pathological features were reviewed. Ten patients with initial diagnoses of LC (n = 2)/CC (n = 8) evolved into UC (n = 7) or CD (n = 3) after a median interval of 14 months (range, 2-44 months). Among these, 4 patients with LC/CC evolving into IBD also had recurrent CC in a quiescent phase of IBD. Seventeen patients with initial diagnosis of UC (n = 11) or CD (n = 6) developed LC (n = 6)/CC (n = 11) after a median interval of 108 months (range, 15-548 months). IBD patients with initial presentation of LC/CC were significantly older than those who developed LC/CC after onset of IBD (66.5 versus 34.0 years old, P = .001). The interval time between LC/CC to IBD was significantly shorter than that of IBD to LC/CC (14 versus 108 months, P = .007). Quiescent UC with superimposed CC was the most common pattern (n = 8). Patients with CD had shorter interval time to develop LC/CC than UC patients, although it was not statistically significant (60.5 versus 139 months, P = .14). Endoscopically, most patients that started with LC/CC had unremarkable findings, but 11 of 17 patients who developed LC/CC after IBD showed quiescent chronic colitis. Histologically, LC/CC patients with diagnosis of IBD, either before or after, more frequently show active inflammation. Chronicity was more commonly seen in biopsy of LC/CC patients with a history of IBD. Our study found that IBD patients with initial presentation of LC/CC tend to occur in older age, with shorter interval time and frequent active inflammation in initial LC/CC. These findings suggest that LC/CC may be a spectrum of IBD as the initial presentation in a subset of older IBD patients. On the other hand, IBD patients can develop LC/CC associated with chronic mucosal injury many years after the onset of IBD (typically with >10 years interval time while patients are in remission phase), for which these 2 processes seem unrelated to each other.

Retrospective study recommends endoscopy when diagnosing lymphocytic colitis or eosinophilic gastrointestinal disorder in children with abdominal pain.

AIM: This study assessed the prevalence, clinical presentation and outcome of lymphocytic colitis (LC) and eosinophilic gastrointestinal disease (EGID) in children with severe, recurrent abdominal pain (RAP), by describing the predominant symptoms, diagnostic approaches and treatment options. METHODS: We performed a retrospective follow-up study at a Danish regional hospital by reviewing the histology reports of the children who had undergone gastrointestinal endoscopy for RAP. Data were retrieved from the medical records of those who met the diagnostic criteria for LC and, or, EGID from 2011 to 2016. The study population comprised 381 patients who underwent a diagnostic process to clarify RAP. RESULTS: A total of 74 patients (39 females) aged 2-17 years, with severe RAP as the most predominant symptom underwent gastrointestinal endoscopy. This identified 16/74 (21.6%) with LC (n = 6) and, or, EGID (n = 11), which equated to 4.2% with RAP. No biochemical patterns of abnormalities were found. Medical treatment and, or, diet generally induced and maintained clinical remission. CONCLUSION: We found 16 children with LC and, or, EGID. The predominant symptom was severe RAP. All patients had a macroscopically normal mucosa at endoscopy, a specific histopathological feature and no characteristic biochemical findings. Endoscopy should be considered in these cases.

Lymphocytic colitis: pathologic predictors of response to therapy.

Although the presence of intraepithelial lymphocytosis with surface epithelial damage is a unifying feature of lymphocytic colitis, there are nonclassical features that create morphologic heterogeneity between cases. Limited data on the significance of these secondary histologic features are available. Cases of lymphocytic colitis diagnosed between 2002 and 2013 were identified using the Research Patient Data Registry of a tertiary referral center. Diagnostic biopsy slides were reviewed and evaluated for histologic features of lymphocytic colitis. Clinical data including type of therapy and response to treatment were collected. χ2 Test (or Fisher exact test) and logistic regression analysis were used where appropriate. Thirty-two cases of lymphocytic colitis with complete clinical data and slides available for review were identified. The mean age was 56.4 years, and the female-to-male ratio was 3:2. Eleven patients improved with minimal intervention (group 1), 14 patients responded to steroid therapy (group 2), and 7 patients responded to mesalamine, bismuth subsalicylate, and/or cholestyramine therapy (group 3). Histologic differences in the characteristics of the subepithelial collagen table (P = .018), the severity of lamina propria inflammation (P = .042), and the presence of eosinophil clusters (P = .016) were seen between groups 2 and 3. Patients in group 1 were more likely to have mild crypt architectural distortion in their biopsies than patients in groups 2 and 3. Lymphocytic colitis is a heterogeneous disease, and the evaluation of histologic factors may help identify various subtypes and predict therapy response.

Lymphocytic colitis complicated by a mass in the terminal ileum.

Lymphocytic colitis is a chronic inflammatory disease affecting the bowel. The clinical course of lymphocytic colitis is believed to be benign with watery diarrhoea. We report herein what is, to the best of our knowledge, the first case of lymphocytic colitis complicated by a terminal ileal mass. A 23-year-old man presented with diarrhoea. Blind biopsies of samples taken from the terminal ileum, caecum and ascending colon showed features of lymphocytic colitis. He declined treatment with budesonide or 5-aminosalicylates. He presented 14 months later with pain over the right lumbar region and nausea. Computed tomographic enteroclysis showed a focal soft tissue enhancing mass at the terminal ileum. Excision of the soft tissue mass revealed that it was reactive nodular lymphoid hyperplasia with fibrous granulation tissue. In conclusion, an untreated lymphocytic colitis may result in the formation of an inflammatory mass lesion.

Association of lymphocytic colitis and lactase deficiency in pediatric population.

Characterized by colonic mucosa intraepithelial lymphocytosis, lymphocytic colitis is primarily an entity presented in the middle-aged to elderly patient population. Very few large series of lymphocytic colitis of childhood occurrence are available in the medical literature. Ten cases each of lymphocytic colitis and of colonic lymphocytosis of other diagnosis, all with duodenal disaccharidases analysis data, were collected from the files of our institution. The electronic medical records were reviewed and multiple variables were analyzed. The ten patients with lymphocytic colitis presented with diarrhea. Of these, three had abdominal pain. The age range was 2-18 years. Nearly all patients were Caucasian (90%) and 70% were female. Endoscopically, most had normal appearing colonic mucosa. Significant past medical history, family medical history and associated comorbidities included celiac disease, Down syndrome, juvenile arthritis and other autoimmune diseases. Interestingly, the most revealing observation was that the majority of cases (80%) were associated with lactase deficiency and, for the most part, gastrointestinal symptoms improved simply by treatment with Lactaid or avoidance of dairy products. This association is statistically significant. Our clinicopathological study indicates that the typical pediatric patient is a female Caucasian. A large of portion of the patients had associated lactase deficiency and improved on Lactaid supplement alone.

Microscopic colitis: is it a spectrum of inflammatory bowel disease?

Lymphocytic and collagenous colitis are forms of microscopic colitis which typically presents in elderly patients as chronic watery diarrhea. The association between microscopic colitis and inflammatory bowel disease is weak and unclear. Lymphocytic colitis progressing to ulcerative colitis has been previously reported; however there is limited data on ulcerative colitis evolving into microscopic (lymphocytic or collagenous) colitis. We report a series of six patients with documented ulcerative colitis who subsequently were diagnosed with collagenous colitis or lymphocytic colitis suggesting microscopic colitis could be a part of the spectrum of inflammatory bowel disease. The median duration of ulcerative colitis prior to being diagnosed with microscopic colitis was 15 years. We noted complete histological and/or symptomatic remission in three out of six cases while the other three patients reverted back into ulcerative colitis suggesting lymphocytic or collagenous colitis could present as a continuum of ulcerative colitis. The exact molecular mechanism of this histological transformation or the prognostic implications is still unclear. Till then it might be prudent to follow up these patients to assess for the relapse of inflammatory bowel disease as well as for dysplasia surveillance.

Clinical presentation, diagnosis, pathogenesis and treatment options for lymphocytic colitis (Review).

Lymphocytic colitis (LC) is characterized by chronic or relapsing non-bloody watery diarrhea and a macroscopically normal colon. However, histopathological examination of colonic biopsy samples reveals an increased intraepithelial infiltration of lymphocytes (≥20/100 enterocytes), and increased inflammatory cells within the lamina propria, but with a normal mucosal architecture. The reported prevalence of LC varies from 14.2 to 45 per 100,000 individuals, while its reported incidence is between 0.6 and 16 per 100,000 individuals. LC has a high rate of spontaneous symptomatic remission and is not associated with an increased risk of colon cancer or inflammatory bowel disease. The diagnosis is based on the histopathological findings. The density of colonic chromogranin A-positive cells provides an effective diagnostic tool with high sensitivity and specificity in both the right and left colon. Gastrointestinal infections, drugs, and/or autoimmunity may trigger chronic colonic low-grade inflammation. Colonic nitric oxide, serotonin and peptide YY (PYY) cell densities are markedly increased in patients with LC. It has been hypothesized that the low-grade inflammation in LC through the endocrine-immune axis causes this increase. It has been postulated further that these abnormalities in the neuroendocrine system of the colon are responsible for the diarrhea observed in patients with LC. The benign course and rate of spontaneous remission of LC denotes that drugs with severe side-effects should be avoided if possible. The drug cost and drug coverage may also be limiting factors for some patients. These aspects should be taken into account when making decisions regarding treatment options.

Impact of current smoking on the clinical course of microscopic colitis.

BACKGROUND: Whether current smoking worsens the clinical course of microscopic colitis (MC) is unknown. The aim was to evaluate the impact of smoking on the clinical course of MC. METHODS: One hundred and eighty-four patients (72% women; age, 62.4 ± 1.1 years) with MC (118 collagenous colitis (CC) and 66 lymphocytic colitis (LC) were evaluated (39 of them were current smokers). In all the patients, smoking habits and clinical data at presentation, response to therapy, and clinical relapses during follow-up were prospectively recorded. Risk factors for clinical relapse were studied in 160 patients after a mean follow-up of 28 ± 1 months. Cox regression analysis was used to adjust for confounding variables. RESULTS: Age at diarrhea onset was 63.0 ± 1.4 years in nonsmokers and 50.4 ± 2.1 years in current smokers (P < 0.001). There was no significant influence of smoking habit on either clinical symptoms at diagnosis or clinical remission rate. Clinical relapse rate was 25.5% for CC and 29.6% for LC, with the mean relapse-free time 28.8 months (95% confidence interval, 26.3-31.4) for CC and 26.9 months (95% confidence interval, 26-30.3) for LC (P = 0.5). Multivariate analysis showed that age at diagnosis (<50 years versus others; adjusted hazard ratio, 2.8; 95% confidence interval, 1.3-6; P = 0.01) was associated with risk of relapse of CC but not LC. Current smoking was not an independent risk factor for either CC or LC relapse. CONCLUSIONS: Active smokers developed MC more than a decade before nonsmokers. Age at diagnosis, but not smoking, was an independent risk factor of relapse in patients with CC.

Non-IBD colitides (eosinophilic, microscopic).

Microscopic colitis includes the terms lymphocytic colitis and collagenous colitis, and is a common cause of chronic diarrhoea in older adults. The incidence of microscopic colitis has increased over time and has reached levels comparable to other forms of inflammatory bowel disease. In this chapter, an updated review on the epidemiology, diagnosis and treatment of microscopic colitis has been provided. There is limited data available about eosinophilic colitis, which is the least common of the eosinophilic GI disorders. It is important to rule out the secondary causes of colonic eosinophilia in patients with suspected eosinophilic colitis.

A retrospective study on a cohort of patients with lymphocytic colitis.

OBJECTIVE: The term "microscopic colitis" includes lymphocytic colitis (LC) and collagenous colitis, bearing common clinical presentation distinguishable only by histopathological examination of colonic biopsies. This study reports on demographic and clinical characteristics, and outcome of a cohort of patients with LC. METHODS: Demographic, clinical and histopathological data were reviewed. Every patient underwent total colonoscopy with multiple biopsies examined by an expert pathologist. Diagnosis of LC was confirmed if histopathological criteria were present. Routine laboratory tests were collected to rule out other diagnosis. RESULTS: We included 80 patients (28 males; mean age: 46.4 years). At diagnosis, 71 patients (88%) reported diarrhea, 46 (58%) abdominal pain, 21 (36%) weight loss, 10 (13%) nausea. Regarding autoimmune or inflammatory diseases accompanying LC, thyroid disorders and celiac disease (CD) ranked first. Moreover, in over 10% of patients who underwent esophagogastroduodenoscopy, duodenal biopsies showed villi alterations classified as Marsh I damage, without clinical and serological data for diagnosis of CD. Mesalazine and oral topical steroids (budesonide or beclomethasone) were used to treat LC in 34 (43%) and 32 (39%) of patients, respectively, with similar percentages of clinical response (approximately 80%). CONCLUSIONS: The need for total colonoscopy with multiple biopsies in all patients with chronic watery diarrhea was confirmed. Since the association between CD and LC exists, additional tests should be performed in patients not responding to gluten-free diet or to LC specific therapy to exclude the other condition. Mesalazine obtained a similar outcome than oral steroids in this cohort.

Refractory lymphocytic enterocolitis and tumor necrosis factor antagonist therapy.

BACKGROUND & AIMS: Lymphocytic enterocolitis is a malabsorptive syndrome characterized by severe small-bowel villous abnormality and crypt hyperplasia and dense infiltrate of lymphocytes throughout the gastrointestinal tract. METHODS: We present 2 patients with lymphocytic enterocolitis refractory to usual medical therapy who were treated with tumor necrosis factor antagonists. RESULTS: Both patients had clinical improvement in diarrheal symptoms and intestinal histologic abnormalities. CONCLUSIONS: Tumor necrosis factor-alpha antagonists such as infliximab or adalimumab may be a new treatment option for patients with severe refractory lymphocytic enterocolitis not responding to corticosteroids.

Colon lesions: pathology specific to women.

Lymphocytic colitis and collagenous colitis represent two conditions that fall under the category of microscopic abnormalities within the lamina propria of the colon. Patients are predominantly women in the sixth decade of life who present with non-bloody watery diarrhea. Few other symptoms exist. Diagnosis is based upon finding characteristic abnormalities in the colonic mucosa, more likely to be found on the right side of the colon than the left. Treatment is symptomatic, although some newer therapies suggest regression of the lesion. Other autoimmune associations have been described, including celiac disease, and appropriate work-up for this condition should be considered for the patient who has seemingly refractory colitis. The natural history is benign, and most patients experience resolution of their symptoms.