Ulcerative Colitis: Microscopic Features
Histologic findings correlate well with the endoscopic appearance and clinical course of UC. The process is limited to the mucosa and superficial submucosa, with deeper layers unaffected except in fulminant disease. In UC, two major histologic features suggest chronicity and help distinguish it from infectious or acute self-limited colitis. First, the crypt architecture of the colon is distorted crypts may be bifid and reduced in number, often with a gap between the crypt bases and the muscularis mucosae. Second, some patients have basal plasma cells and multiple basal lymphoid aggregates. Mucosal vascular congestion, with edema and focal hemorrhage, and an inflammatory cell infiltrate of neutrophils, lymphocytes, plasma cells, and macrophages may be present. The neutrophils invade the epithelium, usually in the crypts, giving rise to cryptitis and, ultimately, to crypt abscesses . Ileal changes in patients with backwash ileitis include villous atrophy and crypt regeneration with increased inflammation, increased neutrophil and mononuclear inflammation in the lamina propria, and patchy cryptitis and crypt abscesses.
Medium-power view of colonic mucosa in ulcerative colitis showing diffuse mixed inflammation, basal lymphoplasmacytosis, crypt atrophy and irregularity, and superficial erosion. These features are typical of chronic active ulcerative colitis.
Dalm In Ulcerative Colitis
Differential Diagnosis of UC-associated Polypoid Dysplasia vs. Sporadic Adenoma: In 1998, our group published the results of a retrospective study of 59 IBD patients , all of whom had at least one benign polypoid dysplastic lesion excised, and in whom the differential diagnosis with an incidental sporadic adenoma was entertained . On the basis of our follow-up data, several clinical, endoscopic and pathologic features were significantly different between probable IBD-associated polypoid dysplastic lesions and sporadic adenomas . Histologically, polypoid dysplastic lesions associated with IBD appear similar to sporadic adenomas in terms of their overall architectural and cytologic features. However, polypoid dysplastic lesions have a higher degree of inflammation within the lamina propria, and usually show a mixture of normal and dysplastic crypts at the surface of the polyp . Stalk dysplasia, if present, should alert the pathologist that dysplasia may be present in the adjacent mucosa and that they are likely dealing with an IBD-associated dysplastic lesion rather than an adenoma. Features such as size, architectural type , degree of dysplasia, and nuclear chromatin pattern are not helpful in distinguishing these two groups of lesions.
TABLE 5 Summary of Differentiating Features between IBD-Associated Polypoid Dysplasia and Sporadic AdenomasTABLE 6 Treatment of DALMs in Ulcerative Colitis
Defective Immune Regulation In Ibd
The mucosal immune system is normally unreactive to luminal contents due to oral tolerance. When soluble antigens are administered orally rather than subcutaneously or intramuscularly, antigen-specific nonresponsiveness is induced. Multiple mechanisms are involved in the induction of oral tolerance and include deletion or anergy of antigen-reactive T cells or induction of CD4+ T cells that suppress gut inflammation that secrete anti-inflammatory cytokines such as interleukin 10, IL-35, and transforming growth factor . Oral tolerance may be responsible for the lack of immune responsiveness to dietary antigens and the commensal microbiota in the intestinal lumen. In IBD this suppression of inflammation is altered, leading to uncontrolled inflammation. The mechanisms of this regulated immune suppression are incompletely known.
What Is Ulcerative Colitis
Ulcerative colitis can begin gradually and become worse over time. However, it can also start suddenly. Symptoms can range from mild to severe. In between periods of flarestimes when people have symptomsmost people have periods of remissiontimes when symptoms disappear. Periods of remission can last for weeks or years. The goal of treatment is to keep people in remission long term.
Clinical Presentation And Differential Diagnosis
Ulcerative colitis phenotypes by Montreal Classification
Extraintestinal manifestations can occur in about a third of patients with ulcerative colitis, and up to a quarter might have extraintestinal manifestations before inflammatory bowel disease diagnosis ., Peripheral arthritis appears to be the most common extraintestinal manifestation primary sclerosing cholangitis and pyoderma gangrenosum are more common in ulcerative colitis than in Crohns disease., The risk of venous thromboembolism in patients with inflammatory bowel disease is increased three to four times, and is greater when the patient is admitted with a flare or being treated with corticosteroids. Clinicians should have a high index of suspicion for venous thromboembolism, and hospitalised patients with ulcerative colitis should be prescribed venous thromboembolism prophylaxis.
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Procedures For The Histological Diagnosis Of Ibd
Because the histological changes in IBD can be focal, serial sections in the tissue block increases diagnostic accuracy and should be performed in order to identify subtle changes . There is no definite number of sections required, but the ESP state that two-three tissue levels is preferred, and if feasible step-section each consisting of five or more sections can be applied . Routine staining with hematoxylin and eosin is appropriate for diagnostic purpose. Whereas special-stains or immunohistochemistry are not needed routinely, they can be used as supplement is selected cases, e.g., a stain for cytomegalovirus might be of relevance .
Moderate Or Extensive Disease
Patients with inflammation proximal to the sigmoid colon or left-sided disease unresponsive to topical agents should receive an oral 5-ASA 5-Aminosalicylic Acid Several classes of drugs are helpful for inflammatory bowel disease . Details of their selection and use are discussed under each disorder . Details of their selection and use are discussed under each disorder . Details of their selection and use are discussed under each disorder or corticosteroid therapy as well as those who are corticosteroid-dependent. Moreover, a combination of immunomodulator and anti-TNF therapy Anti-TNF drugs Several classes of drugs are helpful for inflammatory bowel disease . Details of their selection and use are discussed under each disorder (see Crohn disease treatment and ulcerative colitis… read more is sometimes helpful. Finally, in some patients who fail to respond to corticosteroids, immunosuppressants, or biologics, a trial of the Janus kinase inhibitor tofacitinib, or a trial of sphingosine 1-phosphate receptor modulator ozanimod can be considered.
How Can I Prevent Inflammatory Bowel Disease
While there isnt anything you can do to prevent IBD, certain dietary and lifestyle changes may control the symptoms. You can:
- Eat smaller meals every two to four hours.
- Find healthy ways to manage stress, such as meditation, movement like tai chi, listening to music or going for a walk.
- Get plenty of sleep and stay physically active.
- Keep a food diary to identify foods that trigger IBD flares. You may find you have a food intolerance, such as lactose intolerance. If so, your body has a harder time digesting certain foods, which causes stomach upset.
- Reduce foods that irritate the intestines, such as those that are fibrous, spicy, greasy or made with milk. During flares, choose soft, bland foods that are less inflammatory.
- Cut back on caffeinated, carbonated and alcoholic beverages. Drink more water to prevent dehydration.
Future Directions And Controversies
The number of drugs modulating different disease pathways is expected to expand in the near future. There are at least 27 new drugs for ulcerative colitis with either recently completed or active trials.170 One example is the oral pan-janus kinase inhibitor tofacitinib, which has shown higher rates of clinical remission than placebo in phase 2 studies.171 Etrolizumab, a subcutaneous monoclonal antibody that blocks the 7 subunit of the heterodimeric integrins 47 and E7 achieved higher clinical remission rates than placebo in a phase 2 trial.172 An oral anti-4 integrin therapy significantly increased clinical remission and endoscopic healing in a phase 2 trial.173 An oral drug inhibiting sphingosine-1-phosphate receptors that blocks lymphocyte egress from lymph nodes has also shown efficacy.174 In a small trial of 5-ASA non-responders, curcumin increased endoscopic remission in mild to moderate ulcerative colitis as an add-on therapy.175 Biosimilar biological drugs should decrease the cost of therapy. Results from initial studies with an infliximab biosimilar, CT-P13, have shown efficacy at inducing endoscopic healing in ulcerative colitis.176 However, immunogenicity and efficacy remains a concern particularly in patients switching from the originator to the biosimilar.177
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What Are The Complications Of Ulcerative Colitis
Ulcerative colitis may lead to complications that develop over time, such as
- anemia, a condition in which you have fewer red blood cells than normal. Ulcerative colitis may lead to more than one type of anemia, including iron-deficiency anemia and anemia of inflammation or chronic disease.
- bone problems, because ulcerative colitis and corticosteroids used to treat the disease can affect the bones. Bone problems include low bone mass, such as osteopenia or osteoporosis.
- problems with growth and development in children, such as gaining less weight than normal, slowed growth, short stature, or delayed puberty.
- colorectal cancer, because patients with long-standing ulcerative colitis that involves a third or more of the colon are at increased risk and require closer screening.
In some cases, ulcerative colitis may lead to serious complications that develop quickly and can be life-threatening. These complications require treatment at a hospital or emergency surgery. Serious complications include
Severe ulcerative colitis or serious complications may lead to additional problems, such as severe anemia and dehydration. These problems may require treatment at a hospital with blood transfusions or intravenous fluids and electrolytes.
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Mild To Moderately Active Disease
Am J Gastroenterol.J Crohns Colitis.Gut.Cochrane Database Syst Rev.Am J Gastroenterol.J Crohns Colitis.Cochrane Database Syst Rev.Gut.
Gastroenterology.Cochrane Database Syst Rev.World J Gastroenterol.J Crohns Colitis.Gastroenterology.BMJ.
Gut.Dig Dis Sci.N Engl J Med.
J Crohns Colitis.Am J Gastroenterol.
Pyodermatitis Vegetans Pyostomatitis Vegetans Pyodermatitispyostomatitis Vegetans
Pyodermatitis vegetans , a rare skin manifestation of IBD and often regarded as one of clinical forms of PG, has histopathology similar to pyostomatitis vegetans but with treatment similar to PG . PDV occurs mainly in skin folds such as axillary or inguinal area, but can also be present on the trunk or extremities. These lesions are characterized by pustules that quickly rupture, forming erosions with hemorrhagic ground, developing large raised well-demarcated plaques with surrounding pustules .
Pyodermatitis vegetans was first reported by Hallopeau when he described two patients with unusual pustular dermatosis and oral lesions for which he named pyodermite vegetans . McCarthy proposed the term pyostomatitis vegetans after he observed similar lesions isolated in the oral cavity . Recently these two entities are considered to be variants of the same disease termed pyodermatitispyostomatitis vegetans . PDV and PSV are rare cutaneous manifestation of IBD . In general, bowel disease antedate oral involvement by several years . The rash of PPV has been reported to correlate with underlying bowel disease activity . The pathogenesis of PSV, PDV, or PPV is not clear, but has been hypothesized to be due to aberrant immune responses in IBD to cross-reacting antigens in the skin and bowel resulting in mucocutaneous manifestations .
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Collagenous Lymphocytic Colitis And Variants
ECCO ESP statement 31
The term microscopic colitis describes a clinical pathological entity characterized by three elements: A) a clinical history of chronic watery diarrhea B) a normal or almost normal endoscopic appearance of the colon C) a distinct histologic pattern. The latter can be either that of collagenous colitis or that of lymphocytic colitis
ECCO-ESP statement 32
The diagnosis of collagenous colitis on routinely hematoxylin and eosin stained sections is based on the presence of a thick amorphous hyaline eosinophilic band immediately beneath the surface epithelium of the mucosa. This layer has an irregular, jagged aspect of the lower edge. The thickness is > 10 Î¼m. Its presence is associated with inflammation
ECCO-ESP statement 33
The density of the inflammatory cells in the epithelium and lamina propria is increased in collagenous colitis. The composition of the infiltrate is also changed. Eosinophils may be markedly increased and are sometimes seen infiltrating crypt and surface epithelium together with lymphocytes. The number of mast cells and lymphocytes may also be increased. Neutrophils are often present and may induce occasional crypt abscesses
ECCO-ESP statement 34
The diagnosis of lymphocytic colitis is based on a diffuse increase of intraepithelial lymphocytes in the surface epithelium without associated thickening of the subepithelial collagen accompanied by an increase of lamina propria inflammatory cells
ECCO-ESP statement 35
ECCO-ESP statement 36
What Are Nonsurgical Inflammatory Bowel Disease Treatments
IBD treatments vary depending on the particular type and symptoms. Medications can help control inflammation so you dont have symptoms . Medications to treat IBD include:
- Aminosalicylates minimize irritation to the intestines.
- Antibiotics treat infections and abscesses.
- Biologics interrupt signals from the immune system that cause inflammation.
- Corticosteroids, such as prednisone, keep the immune system in check and manage flares.
- Immunomodulators calm an overactive immune system.
You may also benefit from these over-the-counter IBD treatments:
- Antidiarrheal medication.
- Vitamins and supplements like probiotics.
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Extraintestinal Manifestations And Complications
UC is characterized by immune dysregulation and systemic inflammation, which may result in symptoms and complications outside the colon. Commonly affected organs include: eyes, joints, skin, and liver. The frequency of such extraintestinal manifestations has been reported as between 6 and 47%.
UC may affect the mouth. About 8% of individuals with UC develop oral manifestations. The two most common oral manifestations are aphthous stomatitis and angular cheilitis. Aphthous stomatitis is characterized by ulcers in the mouth, which are benign, noncontagious and often recurrent. Angular chelitis is characterized by redness at the corners of the mouth, which may include painful sores or breaks in the skin. Very rarely, benign pustules may occur in the mouth .
UC may affect the eyes. Inflammation may occur in the interior portion of the eye, leading to uveitis and iritis. Uveitis can cause blurred vision and eye pain, especially when exposed to light . Untreated, uveitis can lead to permanent vision loss. Inflammation may also involve the white part of the eye or the overlying connective tissue , causing conditions called scleritis and episcleritis. Uveitis and iritis are more commonly associated with ulcerative colitis, whereas episcleritis is more commonly associated with Crohn’s disease.
A Close View On Histopathological Changes In Inflammatory Bowel Disease A Narrative Review
Lauge Kellermann1^, Lene Buhl Riis2^
1Department of Gastroenterology, Herlev Hospital, University of Copenhagen 2Department of Pathology, Herlev Hospital, University of Copenhagen , Denmark
Contributions: Conception and design: All authors Administrative support: None Provision of study materials or patients: None Collection and assembly of data: None Data analysis and interpretation: None Manuscript writing: All authors Final approval of manuscript: All authors.
^ORCID: Lauge Kellermann, 0000-0001-8554-3538 Lene Buhl Riis, 0000-0003-4669-3159.
Keywords: Histopathology histological remission histological index Crohns disease ulcerative colitis
Received: 12 January 2021 Accepted: 19 March 2021 Published: 30 March 2021.
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Presence Of Cancer And Dysplasia
Patients with ulcerative pancolitis for more than 8 years are at increased risk of colorectal cancer, approximating 0.5% to 1% per year.57 Those persons with primary sclerosing cholangitis as a complication of their ulcerative colitis have been shown to have an even higher incidence of dysplasia and cancer. Colonoscopic surveillance with random and chromoscopic-directed biopsies has been recommended in patients with long-standing ulcerative colitis. An obstructing lesion and unresectable dysplasia generally warrant surgery. Historically, high-grade dysplasia and multifocal low-grade dysplasia were widely accepted as clear indications for colectomy because of the high rate of an occult malignancy within the colon.8,9 However, there are circumstances in which dysplastic lesions within a field of normal colonic mucosa can be adequately managed endoscopically.10 This is an evolving area of management that requires a clear understanding of the lesion itself, the patients disease course, and the comfort of the treating physicians.
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Cytomegalovirus Infection And Uc
In patients with UC, the risk for reactivation of latent cytomegalovirus infection is a common complication, particularly in those with steroid-resistant disease . On routine H& E stained slides, CMV typically presents as large cells, two- to four-fold larger than normal, with large amphophilic intranuclear inclusions, surrounded by a clear halo, and smaller cytoplasmic inclusions. However, CMV colitis in IBD patients tends to present with atypical, small viral inclusions, often lacking the characteristic owl-eye appearance, and it mostly affects endothelial cells in granulation tissue in ulcers . Therefore, CMV reactivation should be actively sought in all patients with severe colitis refractory to immunosuppressive therapy and on biopsies with prominent granulation tissue associated with large ulcers. Because the infected cells are usually scarce on limited biopsy material and morphologically less characteristic they may be missed on routine H& E stains. Immunohistochemistry, using monoclonal antibodies directed against CMV immediate early antigen, increases the diagnostic yield in comparison with H& E staining. Semiquantitative immunohistochemistry, reporting the number of infected cells and/or the number of CMV positive biopsy fragments, may have a predictive value .
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