Collagenous colitis associated with novel sprue-like intestinal diseases.

Almost a half-century ago, an unusual and distinct form of colitis was first recognized, collagenous colitis, characterized by sub-epithelial trichrome-positive deposits having the ultrastructural features of collagen. Later, other reports documented more extensive collagenous dis-ease in these patients, sometimes in the stomach and small bowel, a close linkage with other forms of microscopic colitis and its association with celiac and other immune-mediated diseases. Moreover, emerging genetic methods permitted large studies of collagenous colitis to complement these intriguing clinical and pathological studies. Finally, recent and related studies have further demonstrated these immune-based forms of colitis, with new sprue-like intestinal diseases caused by novel medications, recently detected viral infections and vaccinations.

Segmental Colitis Associated with Diverticulosis (SCAD).

PURPOSE OF REVIEW: A distinctive, possibly "novel" form of a segmental inflammatory colonic disease process associated with diverticular disease (so-called SCAD or segmental-colitis-associated-diverticulosis) is reviewed. RECENT FINDINGS: Although this phenotype of inflammatory colonic disease was initially recognized decades ago, mainly in the elderly, recent evidence from long term natural history studies along with meta-analyses confirms that its clinical course is usually benign and drug-responsive. Interestingly, its appearance in some treated with monoclonal agents (eg., ipilimumab associated colitis) or infected with coronavirus-19 may have critical implications for its pathogenesis. This review further explores the implications of recognition of this pattern of colonic inflammatory disease, with relevance for physicians involved in both clinical practice and clinical trials of newer therapeutic agents.

Challenges in gluten-free diet in coeliac disease: Prague consensus.

BACKGROUND: New treatments in coeliac disease are being vigorously pursued to either replace or facilitate the difficult-tofollow gluten-free diet. DESIGN: The present review intends to summarise the challenges in gluten-free diet adherence during the transitional period, as reflected in the last Prague consensus, published in 2016. RESULTS: The honourable panel members recommended that dietary adherence and the consequences of nonadherence represent key components for discussion in the transitional period setting. CONCLUSIONS: There are numerous difficulties in adhering to gluten withdrawal, but the transition period from adolescence to young adulthood is considered a fragile and high-risk period for intentional and unintentional gluten intake.

Correction: Heterogeneity in Comparisons of Discontinuation of Tumor Necrosis Factor Antagonists in Rheumatoid Arthritis-A Meta-Analysis.

[This corrects the article DOI: 10.1371/journal.pone.0168005.].

Segmental colitis associated diverticulosis syndrome.

Segmental colitis associated diverticulosis (SCAD) has become increasingly appreciated as a form of inflammatory disease of the colon. Several features suggest that SCAD is a distinct disorder. SCAD tends to develop almost exclusively in older adults, predominately, but not exclusively, males. The inflammatory process occurs mainly in the sigmoid colon, and usually remains localized to this region of the colon alone. SCAD most often presents with rectal bleeding and subsequent endoscopic visualization reveals a well localized process with non-specific histopathologic inflammatory changes. Granulomas are not seen, and if present, may be helpful in definition of other disorders such as Crohn's disease of the colon, an entity often confused with SCAD. Bacteriologic and parasitic studies for an infectious agent are negative. Normal rectal mucosa (i.e., "rectal sparing") is present and can be confirmed with normal rectal biopsies. SCAD often resolves spontaneously without treatment, or completely after a limited course of therapy with only a 5-aminosalicylate. Recurrent episodes may occur, but most often, patients with this disorder have an entirely self-limited clinical course. Occasionally, treatment with other agents, including corticosteroids, or surgical resection has been required.

Celiac disease: a disorder emerging from antiquity, its evolving classification and risk, and potential new treatment paradigms.

Celiac disease is a chronic genetically based gluten-sensitive immune-mediated enteropathic process primarily affecting the small intestinal mucosa. The disorder classically presents with diarrhea and weight loss; however, more recently, it has been characterized by subclinical occult or latent disease associated with few or no intestinal symptoms. Diagnosis depends on the detection of typical histopathological biopsy changes followed by a gluten-free diet response. A broad range of clinical disorders may mimic celiac disease, along with a wide range of drugs and other therapeutic agents. Recent and intriguing archeological data, largely from the Gobleki Tepe region of the Fertile Crescent, indicate that celiac disease probably emerged as humans transitioned from hunter-gatherer groups to societies dependent on agriculture to secure a stable food supply. Longitudinal studies per-formed over several decades have suggested that changes in the prevalence of the disease, even apparent epidemic disease, may be due to superimposed or novel environmental factors that may precipitate its appearance. Recent therapeutic approaches are being explored that may supplement, rather than replace, gluten-free diet therapy and permit more nutritional options for future management.

Prescriber preference for a particular tumour necrosis factor antagonist drug and treatment discontinuation: population-based cohort.

OBJECTIVE: To assess the effect of physician preference for a particular tumour necrosis factor α (TNF) antagonist on the risk of treatment discontinuation in rheumatoid arthritis. DESIGN: Population-based cohort study. SETTING: British Columbia administrative health data (inpatients, outpatients and pharmacy). PARTICIPANTS: 2742 British Columbia residents who initiated a first course of a TNF antagonist between 2001 and December 2008, had been diagnosed with rheumatoid arthritis, and were treated by 1 of 58 medium-volume to high-volume prescribers. INDEPENDENT VARIABLE: A level of physician preference for the drug (higher or lower) was assigned based on preceding prescribing records of the care-providing physician. Higher preference was defined as at least 60% of TNF antagonist courses initiated in the preceding year. Sensitivity analysis was conducted with different thresholds for higher preference. MAIN OUTCOME MEASURE: Drug discontinuation was defined as a drug-free interval of 180 days or switching to another TNF antagonist, anakinra, rituximab or abatacept. The risk of discontinuation was compared between different levels of physician preference using survival analysis. RESULTS: Higher preference for the prescribed TNF antagonist was associated with improved persistence with the drug (4.28 years (95% CI 3.70 to 4.90) vs 3.27 (2.84 to 3.84), with log rank test p value of 0.017). The adjusted HR for discontinuation was significantly lower in courses of drugs with higher preference (0.85 (0.76 to 0.96)). The results were robust in a sensitivity analysis. CONCLUSIONS: Higher physician preference was associated with decreased risk of discontinuing TNF antagonists in patients with rheumatoid arthritis. This finding suggests that physicians who strongly prefer a specific treatment help their patients to stay on treatment for a longer duration. Similar research on other treatments is warranted.

Developments in the treatment of moderate to severe ulcerative colitis: focus on adalimumab.

In selected patients with moderate to severe active ulcerative colitis who have failed to respond or are poorly responsive to standard pharmacologic forms of treatment with corticosteroids and immunosuppressive agents, therapy with a biological agent may be considered. While infliximab is an established tumor necrosis factor blocker and has a longer history of clinical use, adalimumab is an alternative in the same class and may be employed as an initial biological agent, if indicated for treatment of the disease. Adalimumab may have special appeal to stable users able to self-inject in a home setting rather than a centralized infusion center. Short-term adverse effects have been limited, but long-term adverse events can be serious and remain less well defined. Recently, another agent, subcutaneous golimumab, has also been reported to induce and maintain clinical response and remission in clinical trials, but a large experience has not been accumulated to date in clinical practice. In the future, other biological agents with novel and distinct mechanisms of therapeutic action may become available.

Triple metachronous colon cancer.

A 72-year-old male with an early stage "node-negative" sigmoid colon cancer developed 2 separate "node-negative" early stage colon cancers during a subsequent colonoscopy surveillance regimen, the first in the descending colon 7 years later, and the second in the cecum almost 14 years after the first cancer was resected. After the initial symptomatic cancer, all subsequent neoplastic disease, including malignant cancers were completely asymptomatic. This entity, multiple primary cancers, likely reflected the use of a colonoscopic surveillance regimen.

Multiple sclerosis and inflammatory bowel diseases: what we know and what we would need to know!

Multiple sclerosis (MS) is a demyelinating disorder of the central nervous system (CNS) but the causes have not been defined. The disease process appears to involve interplay between environmental factors and certain susceptibility genes. It is likely that the identification of the exact etiological mechanisms will permit the development of preventive and curative treatments. Evaluation of several diseases found to be more often associated than by chance alone may reveal clues to the etiology of those disorders. An association between MS and inflammatory bowel diseases (IBD) was suggested by the observation of an increased incidence of IBD among MS patients. A problem in the interpretation of the data rests, in part, with the observation that abnormal findings in brain magnetic resonance imaging (MRI) may be reported as MS in IBD patients. Defining the limits between incidental MRI findings and findings compatible with MS has resulted in further exploration of this possible association.

Celiac disease: prevalence, diagnosis, pathogenesis and treatment.

Celiac disease (CD) is one of the most common diseases, resulting from both environmental (gluten) and genetic factors [human leukocyte antigen (HLA) and non-HLA genes]. The prevalence of CD has been estimated to approximate 0.5%-1% in different parts of the world. However, the population with diabetes, autoimmune disorder or relatives of CD individuals have even higher risk for the development of CD, at least in part, because of shared HLA typing. Gliadin gains access to the basal surface of the epithelium, and interact directly with the immune system, via both trans- and para-cellular routes. From a diagnostic perspective, symptoms may be viewed as either "typical" or "atypical". In both positive serological screening results suggestive of CD, should lead to small bowel biopsy followed by a favourable clinical and serological response to the gluten-free diet (GFD) to confirm the diagnosis. Positive anti-tissue transglutaminase antibody or anti-endomysial antibody during the clinical course helps to confirm the diagnosis of CD because of their over 99% specificities when small bowel villous atrophy is present on biopsy. Currently, the only treatment available for CD individuals is a strict life-long GFD. A greater understanding of the pathogenesis of CD allows alternative future CD treatments to hydrolyse toxic gliadin peptide, prevent toxic gliadin peptide absorption, blockage of selective deamidation of specific glutamine residues by tissue, restore immune tolerance towards gluten, modulation of immune response to dietary gliadin, and restoration of intestinal architecture.

Celiac disease and selected long-term health issues.

Celiac disease is a genetically-based and immunologically-mediated systemic disorder, affecting primarily the small intestine in adults. About 0.5-1% of most populations studied are affected, with up to 2% in Finland. In families, specifically first-degree relatives, up to 20% may have the disease. Despite increased awareness among physicians and the public, celiac disease is still markedly under-diagnosed at all ages, including the elderly. Although serological screening is now widely used, celiac disease remains a biopsy-defined disorder, and a critical element to the correct diagnosis is documentation of a response to a gluten-free diet (since it is a gluten-sensitive disease). Sometimes, after the diagnosis has been established with a treatment response, changes re-appear and seem resistant to a gluten-free diet. Usually, poor or limited diet compliance, possibly from an unrecognized gluten source is responsible. In others, another superimposed cause, such as an infectious agent, could be important. Finally, another associated disease causing similar clinical and biopsy features or, alternatively, a complicating disorder may develop, such as a lymphoma. Some with biopsy features suggestive of celiac disease may not respond to a gluten-free diet. These may not have celiac disease at all, but instead, a sprue-like intestinal disease, or so-called unclassified sprue.

Long-term natural history and complications of collagenous colitis.

Microscopic forms of colitis have been described, including collagenous colitis, a possibly heterogeneous disorder. Collagenous colitis most often appears to have an entirely benign clinical course that usually responds to limited treatment. Sometimes significant extracolonic disorders, especially arthritis, spondylitis, thyroiditis and skin disorders, such as pyoderma gangrenosum, dominate the clinical course and influence the treatment strategy. However, rare fatalities have been reported and several complications, some severe, have been attributed directly to the colitis. Toxic colitis and toxic megacolon may develop. Concomitant gastric and small intestinal inflammatory disorders have been described including celiac disease and more extensive collagenous inflammatory disease. Colonic ulceration has been associated with the use of nonsteroidal anti-inflammatory drugs, while other forms of inflammatory bowel disease, including ulcerative colitis and Crohn disease, may evolve directly from collagenous colitis. Submucosal 'dissection', colonic fractures, or mucosal tears and perforation, possibly from air insufflation during colonoscopy, have been reported. Similar changes may result from increased intraluminal pressures that may occur during radiological imaging of the colon. Neoplastic disorders of the colon may also occur during the course of collagenous colitis, including colon carcinoma and neuroendocrine tumours (ie, carcinoids). Finally, lymphoproliferative disease has been reported.

Use of the tumor necrosis factor-blockers for Crohn's disease.

The use of anti-tumor necrosis factor-α therapy for inflammatory bowel disease represents the most important advance in the care of these patients since the publication of the National Co-operative Crohn's disease study thirty years ago. The recommendations of numerous consensus groups worldwide are now supported by a wealth of clinical trials and several meta-analyses. In general, it is suggested that tumor necrosis factor-α blockers (TNFBs) are indicated (1) for persons with moderately-severe Crohn's disease or ulcerative colitis (UC) who have failed two or more causes of glucocorticosteroids and an acceptably long cause (8 wk to 12 wk) of an immune modulator such as azathioprine or methotrexate; (2) non-responsive perianal disease; and (3) severe UC not responding to a 3-d to 5-d course of steroids. Once TNFBs have been introduced and the patient is responsive, therapy given by the IV and SC rate must be continued. It remains open to definitive evidence if concomitant immune modulators are required with TNFB maintenance therapy, and when or if TNFB may be weaned and discontinued. The supportive evidence from a single study on the role of early versus later introduction of TNFB in the course of a patient's illness needs to be confirmed. The risk/benefit profile of TNFB appears to be acceptable as long as the patient is immunized and tested for tuberculosis and viral hepatitis before the initiation of TNFB, and as long as the long-term adverse effects on the development of lymphoma and other tumors do not prone to be problematic. Because the rates of benefits to TNFB are modest from a population perspective and the cost of therapy is very high, the ultimate application of use of TNFBs will likely be established by cost/benefit studies.

Duplicated appendix complicated by appendiceal cancer.

A 37-year old male presented with an acute abdomen suggestive of an appendiceal perforation. Urgent laparotomy showed a duplicated appendix with one of the lumens involved with appendicitis and a focal peri-appendicular abscess while the other lumen had a localized appendiceal cancer. Recognition of congenital intestinal duplications in adults is important to avoid serious clinical consequences.