Systematic review: Histological remission in inflammatory bowel disease. Is ‘complete’ remission the new treatment paradigm? An IOIBD initiative

AbstractBackground and aimsAdvances in the medical management of inflammatory bowel disease (IBD) have altered treatment targets. Endoscopic mucosal healing is associated with better outcomes in IBD, though less is known about the significance of achieving histological remission. Our aim was to perform a systematic review to investigate whether histological or ‘complete’ remission constitutes a further therapeutic target in IBD.MethodsA bibliographic search was performed on the 1st of October 2013 and subsequently on the 1st of March 2014 of online databases (OVID SP MEDLINE, OVID EMBASE, National Pubmed Central Medline, Cochrane Library, ISI, conference abstracts), using MeSH terms and key words: (“inflammatory bowel diseases” OR “crohn disease” OR “ulcerative colitis” OR “colitis”) AND (“mucosal healing” OR “histological healing” OR “pathological healing” OR “histological scoring” OR “pathological scoring”).ResultsThe search returned 2951 articles. 120 articles were cited in the final analysis. There is no validated definition of histological remission in IBD. There are 22 different histological scoring systems for IBD, none of which are fully validated. Microscopic inflammation persists in 16–100% of cases of endoscopically quiescent disease. There is evidence that histological remission may predict risk of complications in ulcerative colitis beyond endoscopic mucosal healing, though data are scarce in Crohn's disease.ConclusionsHistological remission in IBD represents a target distinct from endoscopic mucosal healing, not yet routinely sought in clinical trials or practice. There remains a need for a standardized and validated histological scoring system and to confirm the prognostic value of histological remission as a treatment target in IBD

Outcome measurement in clinical trials for Ulcerative Colitis: towards standardisation

Clinical trials on novel drug therapies require clear criteria for patient selection and agreed definitions of disease remission. This principle has been successfully applied in the field of rheumatology where agreed disease scoring systems have allowed multi-centre collaborations and facilitated audit across treatment centres. Unfortunately in ulcerative colitis this consensus is lacking. Thirteen scoring systems have been developed but none have been properly validated. Most trials choose different endpoints and activity indices, making comparison of results from different trials extremely difficult. International consensus on endoscopic, clinical and histological scoring systems is essential as these are the key components used to determine entry criteria and outcome measurements in clinical trials on ulcerative colitis. With multiple new therapies under development, there is a pressing need for consensus to be reached

Death from colonic disease in epidermolysis bullosa dystrophica

BACKGROUND: Squamous cell carcinomas and renal failure were reported the causes of death in patients with recessive dystrophic epidermolysis bullosa (RDEB). Death from colonic disease in epidermolysis bullosa (EB) is never reported. CASE PRESENTATION: We demonstrate a male patient with RDEB. He suffered megacolon due to fecal impaction and died from sigmoid colon perforation with peritonitis at age 35 years. CONCLUSION: Constipation is a common clinical feature of RDEB, but fetal complications of chronic constipation are rarely reported. To the author's best knowledge, it has not been reported or recognized in the English literature previously. The aggressive assessment of constipation with fecal impaction is recommended in patients with RDEB

Why is it so difficult to evaluate faecal microbiota transplantation as a treatment for ulcerative colitis?

Faecal microbiota transplantation (FMT) has recently re-emerged as a viable therapeutic option for colonic disorders. Its efficacy has been proved in the treatment of Clostridium difficile infection which has encouraged research into the use of FMT for other disorders involving gut dysbiosis, such as ulcerative colitis (UC), a chronic inflammatory disease characterized by relapsing and remitting colonic inflammation. Although the FMT protocol for C. difficile treatment is well established, there are numerous additional factors to consider when applying FMT to treat inflammatory diseases. Various studies have attempted to address these factors but technical inconsistency between reports has resulted in a failure to achieve clinically significant findings. Case reports of FMT in UC have shown favorable outcomes yet demonstrating these effects on a larger scale has proved difficult. The following review aims to explore these issues and to analyze why they may be hindering the progression of FMT therapy in UC

What's app? Electronic health technology in inflammatory bowel disease

Electronic health (eHealth) data collection is increasingly used in many chronic illnesses, to track pattern of disease. eHealth systems have the potential to revolutionize care. Inflammatory bowel disease (IBD) is a paradigm for such an approach: this is a chronic disease that usually affects young and technologically literate patient population, who are motivated to be involved in their own care. A range of eHealth technologies are available for IBD. This review considers the strengths and weaknesses of 7 platforms that focus on patient-provider interaction. These have been developed in Denmark, United States, the Netherlands, and the United Kingdom, demonstrating an international interest in this form of technology and interaction. Not only do these technologies aim to improve care but they also have the potential to collect large amounts of information. Information includes demographics and patient reported outcomes (symptoms, quality of life), quality of care (steroid use, among other metrics) and outcomes such as hospitalization. These data could inform quality improvement programmes to improve their focus. eHealth technology is also open to machine learning to analyze large data sets, through which personalized algorithms may be developed

Why is it so difficult to evaluate faecal microbiota transplantation as a treatment for ulcerative colitis?

Faecal microbiota transplantation (FMT) has recently re-emerged as a viable therapeutic option for colonic disorders. Its efficacy has been proved in the treatment of Clostridium difficile infection which has encouraged research into the use of FMT for other disorders involving gut dysbiosis, such as ulcerative colitis (UC), a chronic inflammatory disease characterized by relapsing and remitting colonic inflammation. Although the FMT protocol for C. difficile treatment is well established, there are numerous additional factors to consider when applying FMT to treat inflammatory diseases. Various studies have attempted to address these factors but technical inconsistency between reports has resulted in a failure to achieve clinically significant findings. Case reports of FMT in UC have shown favorable outcomes yet demonstrating these effects on a larger scale has proved difficult. The following review aims to explore these issues and to analyze why they may be hindering the progression of FMT therapy in UC

'Lemonade legs': Why do some patients get profound hypomagnesaemia on proton-pump inhibitors?

Proton pump inhibitors (PPIs) are widely used though an association with hypomagnesaemia and hypocalcaemia has only been described since 2006. Patients typically present after years of stable dosing with musculoskeletal, neurological or cardiac arrhythmic symptoms, but it is likely that many cases are under-recognised. Magnesium levels resolve rapidly on discontinuation of PPI therapy and hypomagnesaemia recurs rapidly on rechallenge with any agent in the class. The cellular mechanisms of magnesium homeostasis are increasingly being understood, including both passive paracellular absorption through claudins and active transcellular transporters, including the transient receptor potential channels (TRPM6) identified in the intestine and nephron. PPIs may alter luminal pH by modulating pancreatic secretions, affecting non-gastric H+K+ATPase secretion, altering transporter transcription or channel function. A small reduction in intestinal absorption appears pivotal in causing cumulative deficiency. Risk factors have been associated to help identify patients at risk of this effect but clinical vigilance remains necessary for diagnosis

Editorial: gut selective immunosuppression-is it a double edged sword? Authors' reply.

The Editorial on the safety of vedolizumab by Sheridan and Doherty in response to our safety review is thoughtful and well balanced, but there are post-marketing data on malignancy after >25000 patient-years of experience with vedolizumab that they do not mentio