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Cureus Dec 2020Crohn's disease (CD) is a transmural inflammatory bowel disease (IBD) that can affect any part of the gastrointestinal (GI) tract. With the disease's progression,... (Review)
Review
Crohn's disease (CD) is a transmural inflammatory bowel disease (IBD) that can affect any part of the gastrointestinal (GI) tract. With the disease's progression, adhesions and transmural fissuring, intra-abdominal abscesses, and fistula tracts may develop. An anal fistula (or fistula-in-ano) is a chronic abnormal epithelial lined tract communicating the anorectal lumen (internal opening) to the perineal or buttock skin (external opening). The risk of fistula development varies from 14%-38%. It can cause significant morbidity, which adversely impacts the quality of life. It is mostly believed that an anal crypt gland infection causes anal abscesses, leading to fistula development. Crohn's disease's pathogenesis involves Th1 and Th17 hypersensitivity due to an unknown antigen within the intestinal mucosa. Evidence to support this review was gathered via the Pubmed database. Search terms used were combinations of "Perianal fistula," "seton," "immunotherapy." Studies were reviewed and cross-referenced for additional reports. Setons are surgical thread loops passed from the external to the internal opening of the fistula tract and exteriorized through the anorectal canal, facilitating abscess drainage and inciting a local inflammatory reaction, thus promoting the resolution of the fistula. Biologicals such as anti-tumor necrosis factor (TNF) antibody (infliximab, adalimumab, certolizumab), anti-IL-12/23 (ustekinumab), and anti-α₄β₇ integrin antibody (vedolizumab) have been approved for Crohn's disease targeting the Th1/Th17-mediated inflammation. Other therapeutic modalities are fistulotomy, cyanoacrylate glue, bioprosthetic plugs, mucosal advancement flap, ligation of inter-sphincteric fistula tract (LIFT), diverting stoma, proctectomy, video-assisted anal fistula treatment (VAAFT), and fistula laser closure (FiLaC). Our review found that chronic seton therapy should be the primary approach, especially if the patient has a perianal abscess. It has a low incidence of re-intervention, recurrent abscess formation, and side-branching of the fistulous tract, with preservation of the fistulous tract's patency and cost-effectiveness. The major disadvantage of seton therapy is the discomfort and time to achieve stability. Among the biologicals, infliximab is the only therapy which has a statistically significant effect on the healing rate of perianal Crohn's fistula compared to placebo, but the major disadvantage associated with anti-TNF as sole therapy is high re-intervention rate, prolong maintenance therapy, high recurrence rate, and severe side effects. We hypothesize that the two aspects should be addressed concurrently to increase the fistula healing or closure rate. First, the seton should be used as initial therapy to maintain tract patency to allow abscess drainage and minimize the intestinal flora colonization within the tract mucosa, thereby leukocytic infiltration and propagation of inflammation within the tract. The second aspect that has to be considered is that we should target the initial stimulation of the Th1/Th17 mediated hypersensitivity instead of a factor/cytokine involved in the inflammation mediation. Although the unknown antigen triggering such hypersensitivity is not clear, we could target the RAR-related orphan receptor γ (RORγ)-T (transcription factor involved in activation of Th17 cells) and the T-bet (transcription factor involved in activation of Th17 cells) within the GI mucosa by a novel target immune therapy.
PubMed: 33415035
DOI: 10.7759/cureus.11882 -
Digestive and Liver Disease : Official... Jan 2021New treatments and therapeutic approaches repeatedly emerged in the field of inflammatory bowel disease.
BACKGROUND
New treatments and therapeutic approaches repeatedly emerged in the field of inflammatory bowel disease.
AIM
to update the French treatment algorithms for Crohn's disease (CD) and ulcerative colitis (UC).
METHODS
A formal consensus method was used to determine changes to the treatment algorithms for various situations of CD and UC. Thirty-seven experts voted on questions that had been drafted by the steering committee ahead of time. Consensus was defined as at least 66% of experts agreeing on a response.
RESULTS
Anti-TNF were reinforced as a first-line therapy rather than the use of immunosuppressant alone. Vedolizumab for UC, ustekinumab for CD took place as second-line maintenance therapy and potentially as a first-line therapy in the setting of unrestricted reimbursement for vedolizumab. Tofacitinib was recommended by the experts in case of vedolizumab failure for UC. Algorithms for complicated CD with abscess, intestinal and complex anal fistula were updated according to recent prospective cohort studies.
CONCLUSION
The changes incorporated to the algorithms provide up-to-date and easy-to-use guidelines to treat patients with IBD.
Topics: Antibodies, Monoclonal, Humanized; Colitis, Ulcerative; Consensus; Crohn Disease; France; Gastrointestinal Agents; Humans; Immunosuppressive Agents; Severity of Illness Index; Tumor Necrosis Factor Inhibitors
PubMed: 33160886
DOI: 10.1016/j.dld.2020.10.018 -
Clinics in Colon and Rectal Surgery Nov 2022Total proctocolectomy and ileal pouch anal anastomosis (IPAA) is the gold standard surgical treatment for the majority (∼90%) of ulcerative colitis (UC) patients. In... (Review)
Review
Total proctocolectomy and ileal pouch anal anastomosis (IPAA) is the gold standard surgical treatment for the majority (∼90%) of ulcerative colitis (UC) patients. In cases of carefully selected Crohn's colitis patients without small bowel or perianal involvement an "intentional IPAA" may be a viable option for disease resection and restoration of intestinal continuity. More commonly, Crohn's is incidentally found either in the resection specimen or, more commonly, when inflammatory complications subsequently arise after pouch construction for UC or indeterminate colitis. These incidental Crohn's pouches may be diagnosed early or late period post-IPAA. Crohn's may manifest within the pouch, in the proximal small bowel, and/or distally in the rectal cuff or anus. Like intestinal Crohn's, Crohn's disease of the pouch may be of an inflammatory, fibrostenosing, or fistulizing phenotype. Treatment depends on the phenotype and includes medical treatment, most commonly in the form of tumor necrosis factor inhibitor medications; however, the newer small molecules offer a potential treatment for these patients. Surgery first entails treating the sequelae of Crohn's and is typically staged. In up to 60% of Crohn's pouches, particularly in fistulizing disease and/or recalcitrant perianal disease, the pouch fails and must be defunctioned or excised. In patients with Crohn's pouches in situ long term, outcomes including quality of life are comparable to patients who underwent IPAA for UC.
PubMed: 36591396
DOI: 10.1055/s-0042-1758139 -
Digestion 2020Inflammatory bowel disease (IBD) is a chronic inflammatory disorder, primarily of, but not restricted to, the gut. Association between IBD and cancer has been clearly... (Review)
Review
BACKGROUND
Inflammatory bowel disease (IBD) is a chronic inflammatory disorder, primarily of, but not restricted to, the gut. Association between IBD and cancer has been clearly established and is uniformly accepted.
SUMMARY
IBD patients are at particular risk for intestinal and extraintestinal cancers. There are 2 underlying mechanisms: (1) IBD-related inflammation triggers initiation and progression of tumor formation. This particularly results in the development of colorectal cancer, small bowel adenocarcinoma, intestinal lymphoma, anal cancer, and cholangiocarcinoma. (2) Immunosuppressive drugs exhibit carcinogenic properties such as shown for azathioprine and anti-TNF promoting lymphoproliferative malignancies and melanoma and nonmelanoma skin cancer. However, within the last years, IBD-related cancer incidence and prevalence have been decreasing, which might be attributed to better treatment options and surveillance strategies. Moreover, novel biological drugs have been introduced in clinical practice and have dramatically changed long-term IBD management. Therefore, we sought to summarize up-to-date knowledge about (1) overall cancer risk; (2) risk and protective factors for cancer development; and (3) inflammation- and immunosuppression-related malignancies in the current anti-TNF era of IBD. Key Messages: Recent studies and meta-analyses questioned the excess rates of cancer in IBD patients. However, IBD still is associated with cancer development due to ongoing intestinal inflammation and the use of potential carcinogenic drugs. Patients should be educated about the increased risk of cancer with IBD and IBD drugs. However, they should also be informed that most malignancy subtypes are possibly preventable by controlling intestinal inflammation and by using adequate screening strategies.
Topics: Humans; Immunosuppressive Agents; Inflammatory Bowel Diseases; Risk Factors; Skin Neoplasms; Tumor Necrosis Factor Inhibitors
PubMed: 32799195
DOI: 10.1159/000509544 -
Drug Safety - Case Reports Sep 2019Toxic epidermal necrolysis (TEN) is an extremely rare condition characterized by separation of dermoepidermal junctions, necrosis, and subsequent detachment of the...
Toxic epidermal necrolysis (TEN) is an extremely rare condition characterized by separation of dermoepidermal junctions, necrosis, and subsequent detachment of the epidermis over large cutaneous areas. TEN can emerge after exposure to certain medications such as allopurinol, aromatic anticonvulsants, NSAIDs, nevirapine, and antibacterial sulfonamides. There is no standard protocol for TEN, and the therapy of choice varies from one patient to another. Some of these therapies include silver-releasing wraps/dressings, glucocorticoids, antibodies to inhibit Fas-mediated keratinocyte apoptosis, and cyclosporine A. A 35-year-old male with an allergy to antibacterial sulfonamides who was being treated for arterial hypertension and hyperuricemia with captopril and allopurinol, respectively, was admitted to hospital. The patient showed skin detachment affecting approximately 95% of his surface area, including his face, upper and lower extremities, trunk, back, oropharyngeal mucosa, anal mucosa, ocular mucosa, and genital mucosa. Intravenous methylprednisolone at a dosage of 40 mg/day for 7 days along with abrasive cures was found to be an appropriate treatment in this case.
PubMed: 31549231
DOI: 10.1007/s40800-019-0101-z -
Therapeutic Advances in Chronic Disease 2019Anti-tumor necrosis factor (TNF) therapy has revolutionized the medical treatment of the inflammatory bowel diseases (IBD), Crohn's disease (CD), and ulcerative colitis.... (Review)
Review
Anti-tumor necrosis factor (TNF) therapy has revolutionized the medical treatment of the inflammatory bowel diseases (IBD), Crohn's disease (CD), and ulcerative colitis. Twenty years ago, infliximab became the first anti-TNF agent approved for IBD. Data from randomized controlled trials, large observational cohort studies, postmarketing registries, and meta-analyses show that infliximab is a very effective treatment for moderate to severe IBD with a good safety profile. Infliximab has been also used to treat pouchitis following an ileal pouch-anal anastomosis (IPAA) after restorative proctocolectomy and to prevent postoperative recurrence following an ileocolonic resection for CD with good results. Nevertheless, up to 30% of patients show no clinical benefit following induction and up to 50% lose response over time. Both these unwanted outcomes can be largely explained by inadequate drug concentrations and frequently by the development of antibodies to infliximab. Loss of response can be managed efficiently and often prevented by applying therapeutic drug monitoring. Recently, the first biosimilars of infliximab have been approved and are utilized in clinical practice with comparable efficacy and safety with the originator. This review will mainly focus on the efficacy of infliximab in IBD.
PubMed: 30937157
DOI: 10.1177/2040622319838443 -
Journal of Clinical Laboratory Analysis May 2021Platelets play a pivotal role in hemostasis. Activated platelets are classified into two groups, according to their agonist response: aggregating and procoagulant... (Review)
Review
Platelets play a pivotal role in hemostasis. Activated platelets are classified into two groups, according to their agonist response: aggregating and procoagulant platelets. Aggregating platelets consist of activated integrin αIIbβ3 and stretch out pseudopods to further attract platelets to the site of injury by connecting with fibrinogen. They mainly gather in the core of the thrombus and perform a secretory function, such as releasing adenosine diphosphate (ADP). Procoagulant platelets promote the formation of thrombin and fibrin by interacting with coagulation factors and can thus be considered as the connector between primary and secondary hemostasis. In addition to their functions in blood coagulation, procoagulant platelets play a proinflammatory role by releasing platelet microparticles and inorganic polyphosphate. Considering these important functions of procoagulant platelets, this subpopulation warrants detailed study to analyze their potential in preventing human diseases. This review summarizes the generation and important characteristics of procoagulant platelets, as well as their potential for preventing the adverse effects associated with current antiplatelet therapies.
Topics: Apoptosis; Biomarkers; Blood Coagulation; Blood Platelets; Humans; Necrosis
PubMed: 33709517
DOI: 10.1002/jcla.23750 -
World Journal of Clinical Cases Sep 2013Pouchitis is not a rare complication that develops after an ileal-pouch anastomosis, performed after colectomy in patients refractory to treatment or with complicated... (Review)
Review
Pouchitis is not a rare complication that develops after an ileal-pouch anastomosis, performed after colectomy in patients refractory to treatment or with complicated ulcerative colitis. This condition may become chronic and unresponsive to medical therapies, including corticosteroids, antibiotics and probiotics. The advent of biological therapies (tumor necrosis factor-α inhibitors) has changed the course of these complications. In particular, in these cases, infliximab (IFX) may represent a safe and effective therapy in order to avoid the subsequent operation for a permanent ileostomy. This article reviews the therapeutic effects of one of the most widely used anti-tumor necrosis factor-α molecules, IFX, for the treatment of complicated pouchitis (refractory to conventional treatment and/or fistulizing).
PubMed: 24303499
DOI: 10.12998/wjcc.v1.i6.191 -
Annals of Gastroenterological Surgery Jul 2018Prevalence of inflammatory bowel disease (IBD), ulcerative colitis and Crohn's disease has dramatically increased in Asian countries in the last three decades. In this... (Review)
Review
Prevalence of inflammatory bowel disease (IBD), ulcerative colitis and Crohn's disease has dramatically increased in Asian countries in the last three decades. In this period, many new medical therapies were introduced for the treatment of IBD, such as immunosuppressants, anti-tumor necrosis factor agents, leukocyte apheresis, anti-integrin antibody, and so on, which have contributed to induce remission and to reduce complications in IBD. As for surgical techniques for Crohn's disease, a stapled functional end-to-end anastomosis and conventional end-to-end anastomosis have similar perianastomotic recurrence rate and reoperation rate. Prospective randomized controlled studies which compare Kono-S anastomosis and stapled side-to-side anastomosis are ongoing. Variant two-stage ileal pouch anal anastomosis (IPAA) and transanal IPAA are new concepts for surgical treatment of ulcerative colitis. Various endoscopic procedures, such as balloon dilation for stenosis or stricture, endoscopic fistulotomy, injection of filling agents, and clipping for fistulas or perforations will be new options in the treatment of Crohn's disease. Adverse effects of preoperative treatments on postoperative complications should also be taken into account to improve surgical outcomes in IBD patients.
PubMed: 30003191
DOI: 10.1002/ags3.12177