Validating microscopic colitis (MC) in Swedish pathology registers.

OBJECTIVE: Microscopic colitis (MC), encompassing collagenous colitis (CC) and lymphocytic colitis (LC), is a diagnosis which relies on histopathologic criteria. This report examines the validity of having a diagnosis of MC in Swedish pathology registers. METHODS: We reviewed patient charts from 215 randomly selected individuals from 15 pathology departments in five healthcare regions in Sweden with a relevant histopathology code for MC on colon biopsies. Information on clinical symptoms and laboratory data were obtained from medical chart review. We obtained sufficient data on 211 individuals for calculating positive predictive values (PPVs) for MC. RESULTS: In total, 200/211 patients with a histopathology diagnosis of MC were confirmed as also having a clinical diagnosis of MC after chart review, yielding a PPV of 95% (95%CI =91-97%). The PPV for CC was 95% (95%CI =87-98%) and 85% for LC (95%CI =78-90%). The median age at biopsy was 67 years (range 17-90 years), and 72% (n = 154) were women. The most common symptoms in patients with MC histopathology were diarrhea (96% of patients), weight loss (24%) and abdominal pain (13%). Four percent (4/111) of patients with available data on stool culture were positive for gastrointestinal pathogens (none had Clostridium difficile). In 81 patients with available celiac serology, five (6%) were positive. Twenty-six percent of all patients had at least one other autoimmune disease, the most frequent being hypothyroidism (8%) and celiac disease (6%). CONCLUSIONS: This study found a high validity for MC as recorded in Swedish pathology registers.

Optimization of a Scoring System to Predict Microscopic Colitis in a Cohort of Patients With Chronic Diarrhea.

GOALS: Our aim was to develop a scoring system to predict risk of microscopic colitis (MC), to identify patients at low risk, potentially avoiding unnecessary biopsies. BACKGROUND: Patients with chronic diarrhea often undergo colonoscopy with biopsy, but few have histologic abnormalities. STUDY: We conducted a retrospective study of patients with chronic diarrhea and a macroscopically normal colonoscopy at our institution over a 9-month period. Multivariable logistic regression assessed the association between predictors and the presence of biopsy-proven MC. RESULTS: The derivation cohort included 617 patients. Median age was 55.1 (39.6 to 68.1) years; 397 (64.3%) were female and 81 (13.1%) had MC. Age ≥55 years, duration of diarrhea ≤6 months, ≥5 bowel movements per day, body mass index <30 kg/m, current smoking, and current use of selective serotonin reuptake inhibitors/serotonin-norepinephrine reuptake inhibitorss and non-steroidal anti-inflammatory drugs were independently associated with MC. A score of ≥10 points in our scoring system, yielded an area under the ROC curve (AUC) of 0.83 with a sensitivity of 93% and specificity of 49% in predicting which patients have MC. The negative predictive value (NPV) was 97.8% (95.0% to 99.1%).In the validation cohort, the scoring system performed similarly (AUC 0.79, sensitivity 91%, specificity 49%, NPV 97%). By avoiding biopsies in patients at low risk of having MC, costs associated with colon biopsies could be reduced by almost 43%. CONCLUSION: This scoring system including 7 clinical variables was able to identify patients unlikely to have MC, with excellent sensitivity, reasonable specificity, and a high NPV, translating into important potential cost savings.

Validation and modification of a diagnostic scoring system to predict microscopic colitis.

OBJECTIVE: Many patients with diarrhoea undergo colonoscopy. If this is macroscopically normal, random biopsies are obtained to rule out microscopic colitis (MC), but most patients have functional disease. Accurate predictors of MC could avoid the need to take biopsies in a substantial proportion of patients, saving money for the health service. We validated a previously described diagnostic scoring system for MC, and incorporated further variables to assess whether this improved performance. MATERIAL AND METHODS: Consecutive adults with loose stools undergoing colonoscopy in Leeds, UK were included. Demographic and symptom data were collected prospectively. The diagnostic scoring system described previously was applied. In addition, the incorporation of further variables, including drugs associated with MC, number of stools, nocturnal passage of stools, and duration of loose stools, into the scoring system was assessed. Sensitivities, specificities, and positive and negative predictive values were calculated. RESULTS: Among 242 patients (mean age 51.0 years, 163 (67.4%) female), 26 (10.7%) of whom had MC, a cut off of ≥4 on the original scoring system had a sensitivity of 92.3% and specificity of 35.2%. Nocturnal passage of stools and duration of loose stools <6 months were significant predictors of MC. Incorporating these variables in a new scoring system with a cut off of ≥6 identified MC with 95.7% sensitivity and 46.0% specificity. CONCLUSIONS: Incorporating nocturnal passage of stools and duration of loose stools into the scoring system may improve ability to predict MC, and avoid random colonic biopsies in a greater proportion of patients with loose stools.

[Microscopic colitis--new insights relevant to clinical practice]. / Mikroskopische Kolitis--neue praxisrelevante Erkenntnisse.

Microscopic colitis is an increasingly recognised chronic inflammatory bowel disease associated with watery, non-bloody diarrhoea. In addition, many patients suffer from abdominal pain, nocturnal diarrhoea, urgency and incontinence. The two traditional histological subtypes are collagenous colitis and lymphocytic colitis. A novel third subgroup is the so-called incomplete microscopic colitis which is clinically indistinguishable. At present, budesonide is the only evidenced-based effective therapy, however many problems in the long-term treatment strategy are still unsolved. The present paper reviews new developments in microscopic colitis which are relevant for clinical practice.

Observer variability in the histopathologic diagnosis of microscopic colitis and subgroups.

The diagnosis of microscopic colitis (MC) is based on histologic findings and includes collagenous colitis (CC) and lymphocytic colitis (LC). Incomplete MC (MCi) denotes patients with chronic diarrhea and a normal endoscopy and morphological changes that do not completely meet the histologic criteria of LC or CC. The aim of this study was to investigate the intraobserver and interobserver agreement on the MC subtypes of CC, LC, and MCi and the ability to discriminate MCi from normal and inflammatory bowel disease/nonspecific reactive changes. A single hematoxylin and eosin-stained specimen from biopsies of the following 5 groups were randomly selected and blinded: CC, LC, MCi, inflammatory bowel disease, and normal. Three pathologists independently reviewed the specimens. The specimens were relabeled and reinterpreted 4 months later. Intraobserver and interobserver agreement was evaluated by κ statistics. κ values for intraobserver agreement were good for 5 diagnostic groups varying from 0.70 to 0.83 and very good when simplifying to only 3 diagnostic groups varying from 0.88 to 0.96, separating MC/MCi from non-MC. κ values for interobserver agreement varied from 0.60 to 0.75 for 5 diagnostic groups and 0.81 to 0.89 for 3 diagnostic groups. The study shows that the intraobserver and interobserver agreement is high for discriminating between MC/MCi and non-MC, whereas the ability to discriminate MCi from CC and LC is lower. A revision and consensus on the histologic criteria of the MC subtypes seem warranted.

Systematic review: are lymphocytic colitis and collagenous colitis two subtypes of the same disease - microscopic colitis?

BACKGROUND: Despite similar clinical symptoms, collagenous colitis (CC) and lymphocytic colitis (LC) are considered two distinct disease entities. AIM: To compare pathoanatomical findings, clinical presentations, risk factors, course of diseases and response to treatment in CC and LC to establish whether they could be subtypes of the same disease, microscopic colitis (MC). METHODS: The MEDLINE was searched for CC, LC and MC, and clinical studies of >20 patients were included. Pooled results with 95% confidence intervals were calculated based on the number of patients. RESULTS: An abnormal number of intraepithelial lymphocytes are found in 45% (40-50%) with CC, and an abnormal subepithelial collagen band in 16% (13-20%) with LC suggesting a histological overlap. The incidence of CC and LC has increased in parallel. Mean age (CC 63 years; LC 60 years) and clinical presentation are indistinguishable, and females are predominant in CC (77%; 75-79%) as well as LC (68%; 66-70%). Risk factors such as nonsteroid anti-inflammatory drugs consumption CC 39% (36-42%); LC 32% (29-35%) are similar and prevalence of concomitant autoimmune diseases such as coeliac disease (CC 5%; CI: 4-6% and LC 7%; CI: 6-9%) do not differ. Bile acid diarrhoea is highly prevalent in CC (41%; 37-45%) and LC (29%; 24-34%). The effect of budesonide is identical. CONCLUSIONS: CC and LC could be considered histological subtypes of the same disease, MC. To facilitate recruitment to clinical trials, all MC patients could be included in future trials and stratified for subtypes.

Observer variability in the histologic diagnosis of microscopic colitis.

BACKGROUND: Microscopic colitis is diagnosed based on histologic criteria. There has been no investigation of the reproducibility of the histologic diagnosis of microscopic colitis. Our aim was to evaluate interobserver and intraobserver variation in this diagnosis. METHODS: Colonic biopsies from 90 subjects (20 lymphocytic colitis, 20 collagenous colitis, 20 inflammatory bowel disease, and 30 normal) were blindly and independently reviewed by 4 gastrointestinal pathologists. The biopsies were classified by each pathologist into 1 of 6 diagnostic categories: lymphocytic colitis, collagenous colitis, active chronic colitis, focal active colitis, normal, or other. The slides were then relabeled and blindly reinterpreted 3 months later. The degree of agreement was determined using kappa statistics (lambda). RESULTS: Interobserver agreement with the 6 diagnostic categories was 69% (kappa = 0.76, 95% CI 0.69, 0.83) and 70% (kappa = 0.71, 95% CI 0.61, 0.79) for the first and second observations, respectively. Interobserver agreement with final diagnostic categories of microscopic colitis versus nonmicroscopic colitis was 91% (kappa = 0.90, 95% CI 0.82, 0.96) and 88% (kappa = 0.83, 95% CI 0.73, 0.92), respectively. Mean intraobserver agreement with the 6 diagnostic categories was 83% (kappa = 0.77). Mean intraobserver agreement with the final diagnostic categories of microscopic colitis versus nonmicroscopic colitis was 95% (kappa = 0.89). CONCLUSIONS: Both interobserver and intraobserver agreement were good in distinguishing among the 6 diagnostic categories, and excellent in distinguishing between microscopic colitis and nonmicroscopic colitis diagnoses. The histologic criteria for microscopic colitis provide for consistent and reproducible interindividual and intraindividual diagnoses in the evaluation of colonic biopsies.

Colitis microscópica: Patogénesis / Microscopic colitis: Pathogenesis

Introducción: Colitis microscópica (CM) es el proceso inflamatorio crónico observado en biopsias del colon de pacientes con diarrea crónica acuosa. Se denomina microscópica porque el diagnóstico es histológico ya que las características microscópicas de la endoscopía del colon son normales. Incluye 2 patrones: Colitis microscópica Linfocítica y la Colítis microscópica Colagenosa. La causa es desconocida y los mecanismos patógenos propuestos señalan un fenómeno inmunológico; de acuerdo a este concepto los autores del presente estudio suponemos que la infiltración linfocítica en la lámina propia podrían corresponder a linfocitos citotóxicos CD8 como ejecutores del daño tisular colónico. Objetivos: Probar la hipótesis de la patogénesis inmunológica de la CM. Material y Método: 38 pacientes con diagnóstico de CM reclutados durante los 4 últimos años en el laboratorio de patología Clínica Ricardo Palma. Se seleccionaron 22 biopsias de colon con lesiones histológicas más severas, correspondientes a 17 pacientes, 5 de ellos tuvieron 2 biopsias en 2 sesiones colonoscópicas, las biopsias fueron fijadas en formol neutro. Y procesadas por el método de inclusión en parafina, tenidas con hematoxilina y eosina y tricrómica de Masson para tejido colágeno. La inmunohistoquímica se hizo en secciones histológicas de 4 y 5 micras de espesor precesadas por el método de la Inmunopereoxidasa. Resultados: 19 biopsias correspondieron a CM Linfocítica y 3 a CM Colagenosa. El CM Linfocítica mostró linfocitosis intraepitelial, daño epitelial distrófico en las áreas de infiltración linfocítica, inflamación de la lámina propia con linfocitos y célula plasmática, membrana basal normal. La CM Colagenosa mostró membrana basal engrosada por la presencia de una banda colágena, linfocitos Intra epiteal leve a moderado vacuolización y frecuente desprendimiento del epitelio cobertor. Los estudios de Inmunohistoquímica fueron positivos en las 22 biopsias estudiadas.

Introduction: Microscopic colitis (MC) is a chronic inflammatory process observed in colon biopsies of patients with chronic aqueous diarrhea. It is called microscopic because diagnosis is determined by histological studies since the microscopic characteristics of the colon endoscopy are normal. Two patterns exist: Lymphocytic Microscopic Colitis and Collagenous Microscopic Colitis. Etiology is unknown, and the proposed pathogenic mechanisms indicate an immunological phenomenon. Based on this, the authors of this study hypothesize that lymphocytic infiltration of the lamina propria could be related to cytotoxic lymphocytes CD8 as causative agents of colon tissue damage. OBJECTIVES: Prove hypothesis of immunological pathogenesis of MC. Apparatus and Methods: Thirty eight (38) patients with diagnosed MC were recruited for the last four years in the Pathology Laboratory at Ricardo Palma University. Twenty two (22) colon biopsies with the most severe histological lesions were selected. Thesebiopsies were obtained from 17 patients: 5 patients had 2 biopsies in 2 colonoscopy sessions. Biopsies were fixed in neutral formaldehyde, processed through the paraffin inclusion method, and stained with hematoxiline-eosine and Masson trichromic to distinguish collagenous tissue. Immunohistochemistry was conducted in 4- or 5-micron-thick histological sectionsprocessed through the immunoperoxidase method. RESULTS: Nineteen (19) biopsies corresponded to Lymphocytic MC and 3 to Collagenous MC. Lymphocytic MC showed intraepithelial lymphocytosis, dystrophic epithelial damage in the areas of lymphocytic infiltration, lamina propria inflammation with lymphocytesand plasma cells, and normal basement membrane. Collagenous MC showed thickened basement membrane due to the presence of a collagenous band, mild to moderate intraepithelial lymphocytosis, vacuolization, and frequent detachment of protective epithelium. Twenty two (22) biopsies were positive in the immunohistochemical...

[Microscopic colitis. A 20 cases series]. / Les colites microscopiques. A propos de 20 cas.

Microscopic colitis are defined as a chronic inflammation of a normal macroscopic colonic mucosa. We report 20 cases of microscopic colitis. Chronic diarrhea revealed the diagnosis in 95% of cases. Endoscopic examination was normal in 95% of patients. We diagnosed collagenous colitis in 65% of cases and lymphocytic colitis in 35% of cases. The treatment was based on sulphasalazine in 16 patients, on 5 aminosalicylic acid in 1 case, on gluten free diet in 2 cases and a symptomatic treatment was prescribed to one patient. A clinical remission was observed in 41.2% of patients taking sulphasalazine.

Atypical forms of microscopic colitis: morphological features and review of the literature.

Microscopic colitis is defined as a syndrome of chronic watery diarrhea with a chronic inflammatory cell infiltrate in the colonic mucosa but without significant abnormalities at colonoscopy. It encompasses at least two histopathologic entities (ie, collagenous and lymphocytic colitis). The recognition and characterization of microscopic colitis has markedly changed the approach to the evaluation and management of chronic diarrhea. The histologic features of collagenous and lymphocytic colitis are well known to most pathologists. By considering the clinical history and symptoms, the pathologist should be able to reach the correct diagnosis in most cases. However, the spectrum of morphologic changes associated with watery diarrhea syndrome appears to be broader than originally thought. Morphologic changes more often associated with chronic inflammatory bowel disease or even chronic ischemic or infectious colitis have been noted in patients with clinically established microscopic colitis. The data presented in this article suggest that microscopic colitis is a heterogeneous entity, which includes both classic and "atypical" forms. Problems arise when cases do not fit the usual pattern or lack some of the findings that are expected. Pathologists should be aware of the presence of atypical forms of microscopic colitis.