Gastroenterol 2024; 166: 87. Open Access! Spotlight (1 page summary)
Key recommendations
AGA recommends metronidazole and/or ciprofloxacin as preferred treatment of pouchitis with duration of treatment 2-4 weeks.
For Crohn’s-like disease of the pouch, AGA guideline recommends using either ileal-release budesonide or advanced immunosuppressive agents (eg. Biological therapies and small molecule therapies)
“In patients with cuffitis, topical therapies should be the first-line therapy, such as mesalamine suppositories, corticosteroid suppositories, or corticosteroid ointment applied directly to the cuff. Biological therapies and small molecule therapies are recommended in refractory cases
Two recent articles review cannabis-related disorders:
DA Gorelik. NEJM 2023; 389: 2267-2275. Cannabis-Related Disorders and Toxic Effects
Background: “In the United States, an estimated 52.4 million persons 12 years of age or older used cannabis in 2021, representing 18.7% of the community-dwelling population in that age group,5 and 16.2 million persons met the diagnostic criteria for cannabis use disorder, which has as its core feature the use of cannabis despite adverse consequences…Cannabis use poses a global disease burden, albeit substantially less than that posed by other psychoactive substances such as alcohol, tobacco (nicotine), opioids, and stimulants.10 The Global Burden of Disease project calculated that cannabis use in 2016 was responsible for an estimated 646,000 years of healthy life lost to disability.”
Key points:
“Cross-sectional surveys suggest that recent cannabis use increases the risk of motor vehicle crashes by 30 to 40%.26 By comparison, a blood alcohol concentration of 0.08% increases the risk of crashes by 250 to 300%.26“
“Cannabis use disorder, like other substance use disorders, is a chronic, relapsing condition.”
“A substantial reduction or a cessation of cannabis use after heavy or long-term use results in a withdrawal syndrome that is usually mild and self-limiting.39…Common psychological symptoms of cannabis withdrawal include depressed mood, anxiety, restlessness, irritability, decreased appetite, and sleep disturbance. Physical signs and symptoms are less common and include abdominal cramps, muscle aches, tremor, headache, sweating, chills, and weight loss. These signs and symptoms typically begin within 1 to 2 days, peak within 2 to 6 days, and last for several weeks…The prevalence of any withdrawal symptoms is almost 50% in persons who were using cannabis daily.”
Neonatal cannabis exposure: “Pregnant persons who use cannabis expose their neonates to cannabis. Such in utero exposure is associated with increased risk among newborns of having low birth weight, being small for gestational age, and being admitted to the neonatal intensive care unit.”
“Cannabinoid hyperemesis syndrome, a form of cyclic vomiting syndrome that is often accompanied by abdominal pain, occurs during or within 48 hours after frequent and heavy cannabis use.75 Cannabinoid hyperemesis syndrome is a major reason for cannabis-related visits to emergency departments, and it accounts for about 10% of patients with cyclic vomiting syndrome.76 Cannabinoid hyperemesis syndrome is distinguished from cyclic vomiting syndrome by its temporal association with cannabis use, relief with hot baths or showers, and resolution with extended abstinence from cannabis…The symptoms of cannabinoid hyperemesis syndrome are treated with benzodiazepines, haloperidol, and topical capsaicin. “
M Camilleri, T Zheng. Clin Gastroenterol Hepatol 2023; 21: 3217-3229. Cannabinoids and the Gastrointestinal Tract This article focuses more on the GI tract effects of cannabinoids.
At a lot of IBD conferences, there is often a lot of focus on health maintenance including discussions on optimizing immunization levels and nutrition. It is often striking how, in comparison, so little attention is focused on emotional health which seems to cause a much greater health burden.
CS Tse et al. Inflamm BowelDis 2024; 30: 150-153. Increased Risks for Suicide, Self-Harm, Substance Use, and Psychiatric Disorders in AdultsWith Inflammatory Bowel Disease: A Nationwide Study in the United States From 2007 to2017
Background: Patients with IBD are also at an increased risk for chronic opioid use, depression, anxiety, sleep disturbance, and disease-related disability (eg, unemployment), all known risk factors for suicide
Methods: This cross-sectional study uses the Nationwide Emergency Department Sample of the Healthcare Cost and Utilization Project (HCUP) as a public domain representing 80% of the U.S. population. This analysis included more than 260 million emergency department visits across the United States from 2007 to 2017.
Key findings:
Inflammatory bowel disease conferred >10-fold risk for suicide deaths, self-harm, substance use, and psychiatric disorders.
The absolute numbers of self-harm rates were low (<1% of all-cause inflammatory bowel disease emergency department visits; total 56 suicide deaths). This amounts to about 5 suicide deaths per year (compared to 0.5 per year for patients with celiac disease.
The risk of self-harm was higher in patients with Crohn’s disease than ulcerative colitis (RR, 3.3; 95% CI, 1.2-5.4), though the suicide risk was not statistically different (RR, 2.3; 95% CI, 0.8-4.5).
From Table 2: RR of self-harm, suicide, psychiatric disorders, and substance use of adults with inflammatory bowel disease compared with celiac disease in the United States from 2007 to 2017. The authors found that rates of self-harm and suicide were the same for patients with celiac disease as the general population (RR 1.0).
My take: Attention to mental health is important component of good care for patients with inflammatory bowel disease.
D Alsoud et al Inflamm Bowel Dis 2024; izad315, https://doi.org/10.1093/ibd/izad315. Real-world Effectiveness and Safety of Risankizumab in Patients with Moderate to Severe Multirefractory Crohn’s Disease: A Belgian Multicentric Cohort Study
Methods: Data from consecutive adult CD patients who started risankizumab before April 2023 were retrospectively collected at 6 Belgian centers. A total of 69 patients (56.5% female, median age 37.2 years, 85.5% exposed to ≥4 different advanced therapies and 98.6% to ustekinumab, 14 with an ostomy) were included.
Key findings:
At week 24, 61.8% (34 of 55) and 18.2% (10 of 55) of patients without an ostomy achieved steroid-free clinical response and remission, respectively.
At week 52, these numbers were 58.2% (32 of 55) and 27.3% (15 of 55), respectively. Endoscopic data were available in 32 patients, of whom 50.0% (16 of 32) reached endoscopic response within the first 52 weeks.
Results in patients with an ostomy were similar (steroid-free clinical response and remission, 42.9% and 14.3%, respectively).
20.3% (14 of 69) of patients underwent CD-related intestinal resectionsand 18.8% (13 of 69) of patients discontinued risankizumab during followup (median 68 weeks).
Risankizumab was well tolerated with no safety issues.
Discussion points: “98.6% of patients in the current study were exposed to ustekinumab compared with less than 20% in the registration trials. This indicates that a previous lack or loss of response to the inhibition of the p40 subunit common to IL-12 and IL-23 does not preclude a potential response from subsequent selective inhibition of IL-23. “
My take: This study shows that risankizumab can be effective in refractory patients, even in those who have received similar type medications (eg. ustekinumab).
Disclaimer: This blog, gutsandgrowth, assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician. Because of rapid advances in the medical sciences, the gutsandgrowth blog cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure. This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.
Methods: “Åkerström et al7 conducted a multi-national population-based cohort study of all patients with a diagnosis of Barrett’s esophagus in the national patient registries of Denmark (2012–2020), Finland (1987–1996 and 2010–2020), Norway (2008–2020), and Sweden (2006–2020). Patients with Barrett’s who underwent anti-reflux surgery (ARS) were compared with non-operated patients, most of whom were presumed to be using anti-reflux medication. The cohort consisted of 33,939 patients with Barrett’s esophagus, 542 (1.6%) of whom had undergone anti-reflux surgery.” Followup was up to 32 years. Mean age in the cohort was 64.3 years.
Key finding: “The main findings of the study were: 1) that the HR of developing EAC [esophageal adenocarcinoma] was actually greater in the ARS [anti-reflux surgery] cohort than in the non-operated cohort HR (adjusted HR 1.9, 95% CI 1.1–3.5); and 2) that the HR did not stabilize with a longer period of follow-up, but instead continued to increase, going from 1.8 (95% CI 0.6–5.0) within 1–4 years of follow-up to 4.4 (95% CI 1.4–13.5) after 10–32 years of follow-up.”
Discussion points:
The editorial suggests that ARS may not actually increase the risk of EAC, but instead the difference may be related to a selection of bias of choosing patients with more severe Barrett’s to have surgery.
For a patient at age 25 years with Barrett’s the cumulative risk of 50 years would translate to a 12% lifetime risk of EAC
The editorial reviews the use of PPIs from the AspECT trial and noted that “high-dose PPI plus low-dose aspirin was more effective than low-dose PPI alone in preventing that composite end point [all-cause mortality, EAC, or high-grade dysplasia]…a large part of the treatment effect was attributable to reduction in all-cause mortality (including cardiovascular) rather than EAC or high-grade dysplasia”
From editorial: Patient’s main reason for undergoing laparoscopic anti-reflux surgery in a community practice: 83 patients in a managed care environment. Data from Vakil et al.6
My take: This article provides good evidence that reflux surgery does not reduce the risk of esophageal adenocarcinoma in those at highest risk. For pediatric patients with severe reflux, this information is helpful for accurate counseling.
Previously, it has been noted that several immune mediated problems paradoxically can be triggered by the use of TNF inhibitors (eg. infliximab, adalimumab) even though these medications are often used to treat these problems (see posts below).
Using 2 nationwide cohorts (Danish & French), Ward et al (Clin Gastroenterol Hepatol 2024; 22: 135-143. Open Access! Tumor Necrosis Factor Inhibitors in Inflammatory Bowel Disease and Risk of Immune Mediated Inflammatory Diseases) report on the associated risk of developing a number of additional immune mediated inflammatory diseases (IMIDs) after treatment with anti-TNF agents for inflammatory bowel disease (IBD). The Danish and French cohorts comprised 18,258 and 88,786 subjects with IBD. Key findings:
Anti-TNF therapy was associated with an increased risk of rheumatoid arthritis, psoriasis, and hidradenitis suppurativa in both the Danish (HR, 1.66) and the French cohort (HR, 1.78), with a pooled HR of 1.76
The absolute risk of IMIDs in the Danish cohort was 5.3/1000 person years compared to 3.8/1000 PY those who had not received anti-TNFs; in the French cohort, the rate in anti-TNF exposed was 5.4/1000 PY compared to 3.0/1000 PY in the unexposed group.
Anti-TNF therapy was also associated with an increased risk of the IMIDs when compared with azathioprine (pooled HR, 2.94).
The results suggest that anti-TNFs paradoxically increase the risk of IMIDs; however, individuals receiving anti-TNFs are likely at higher risk for these disorders and this could be difficult to control for in a retrospective study.
My take: While anti-TNF agents have been a tremendous advance in the treatment of IBD, in a small number of individuals, these agents appear to trigger a paradoxical reaction.
The authors retrospectively utilized the University of Manitoba IBD Epidemiology Database includes all Manitobans diagnosed with IBD between 1984 and 2018 (n=5920). Key findings:
Rates of PPI use in control subjects increased gradually from 1.5% to 6.5% over 15 years
Persons with IBD had a higher rate of PPI use, peaking up to 17% within 1 year of IBD diagnosis with a rate ratio (RR) of 3.1
The authors noted an abrupt increase in PPI use within 6 months of an IBD diagnosis which could indicate that IBD-related symptoms are being mistakenly treated with a PPI or that IBD may increase reflux-related symptoms. Given the higher rate of PPI use in pre-IBD diagnosis patients, compared to controls, the authors note that “it is possible that their [PPI] use enhances the likelihood of an IBD diagnosis by their role in altering the gut microbiota.” In addition, they note that “a case-control study found that PPIs were associated with an increased risk of pediatric IBD” (NR Schwartz et al. J Pediatr Pharmacol Ther 2019; 24: 489-496).
My take: PPIs are being used more frequently. Whether PPIs are detrimental before or after a diagnosis with IBD is not clear.
JCT Lai et al. NEJM 2023; 389: 2377-2385. Case 39-2023: A 43-Year-Old Woman with Chronic Diarrhea, Hair Loss, and Nail and Skin Changes
This case presents a polyposis disorder seen in adults and provides a useful differential diagnosis: autoimmune disorders including IBD, vasculitis, and celiac, primary adrenal insufficiency, heavy metal poisoning, amyloidosis, and cancer. This rare disorder has a reported “5-year mortality of 55%, mostly due to complications such as sepsis and gastrointestinal bleeding”
A few of the images from Figure 2:
Numerous sessile polyps in colonFrom Stomach
ChatGPT’s explanation of Cronkhite-Canada Syndrome:
Cronkhite-Canada syndrome (CCS) is a rare, noninherited, sporadic gastrointestinal polyposis syndrome that affects various parts of the digestive system. It is characterized by the presence of multiple polyps in the stomach and colon, as well as other distinctive features.
Epidemiology: Cronkhite-Canada syndrome is a very rare disorder, with only a few hundred cases reported worldwide. It typically affects older adults, with an average age of onset around 60 years, and there is no known genetic predisposition.
Clinical Presentation: Patients with Cronkhite-Canada syndrome often present with a combination of gastrointestinal and dermatological symptoms. The gastrointestinal manifestations include diarrhea, abdominal pain, weight loss, and protein-losing enteropathy. The dermatological symptoms consist of characteristic changes such as nail atrophy, hyperpigmentation, alopecia (hair loss), and skin hyperpigmentation.
Gastrointestinal Findings:
Polyposis: Multiple [hamartomotous] polyps are found in the stomach and colon. These polyps can vary in size and number.
Diarrhea and Abdominal Pain: Chronic diarrhea and abdominal pain are common symptoms due to the involvement of the digestive tract.
Dermatological Findings:
Nail Changes: Nail atrophy, ridges, and splitting are commonly observed.
Skin Changes: Hyperpigmentation of the skin, especially on the palms and soles, is a distinctive feature.
Alopecia: Hair loss is often present.
Laboratory Findings: Patients with Cronkhite-Canada syndrome may exhibit laboratory abnormalities, including hypoalbuminemia (low levels of albumin in the blood), hypoproteinemia, and electrolyte imbalances due to protein loss in the gastrointestinal tract.
Diagnosis: Diagnosis is based on a combination of clinical presentation, endoscopic findings, and pathology results from biopsies of the affected gastrointestinal tissue.
Treatment: Management of Cronkhite-Canada syndrome involves a multidisciplinary approach. Nutritional support is essential, and patients may require supplementation of protein and nutrients. Corticosteroids are often used to suppress inflammation, and immunosuppressive agents may be considered in refractory cases. Regular surveillance endoscopy is necessary to monitor polyp growth and assess response to treatment.
Patients diagnosed with nonerosive gastroesophageal reflux disease did not have a higher incidence of esophageal adenocarcinoma than the general population in a new study published in the BMJ.
This extensive population-based cohort study leveraged data spanning over three decades from national healthcare registries in Denmark, Finland and Sweden, known for their broad scope and high quality…
The incidence rate of EAC [esophageal adenocarcinoma] among 285,811 patients with nonerosive GERD (no esophagitis, Barrett’s esophagus or other esophageal condition), was 11.0 per 100,000 person-years, similar to that of the general population (BMJ 2023;382:e076017). Moreover, the rate remained stable regardless of the length of follow-up…
Harish K. Gagneja, MD, FACG, AGAF, FASGE, who was not involved in the research, commented that “patients with nonerosive GERD don’t require additional follow-up endoscopies unless they have alarm symptoms such as dysphagia, weight loss or anemia, etc.”…
The findings will need to be confirmed in well-designed studies from other countries. But the large sample size, population-based design, substantial duration of follow-up and inclusion of a contrasting erosive GERD cohort for validation are just some of the study’s strengths, supporting the validity of its findings.
My take: This study indicates that nonerosive reflux was not associated with an increased risk of esophageal adenocarcinoma.
Chen H, et al. NEJM 2023; 389: 1649-1659. Thalidomide for Recurrent Bleeding Due to Small-Intestinal Angiodysplasia
In this multicenter, double-blind, randomized, placebo-controlled trial, 150 adult patients underwent randomization: 51 to the 100-mg thalidomide group, 49 to the 50-mg thalidomide group, and 50 to the placebo group. Thalidomide has antiangiogenic activity, with inhibition of VEGF. It also has many adverse effects of thalidomide including peripheral neuropathy, fatigue, and teratogenic effects.
Key finding:
The percentages of patients with an effective response in the 100-mg thalidomide group, 50-mg thalidomide group, and placebo group were 68.6%, 51.0%, and 16.0%, respectively
Discussion points -(from the associated editorial by Loren Laine): The data for thalidomide for small-intestinal angiodysplasia is “of higher quality than evidence for any other therapy for this indication. In addition,….thalidomide may be disease-modifying, with efficacy persisting after discontinuation. However, many clinicians will still use somatostatin analogues first” due to convenience and safety.
My take: I am glad this is a rare problem in pediatrics. I am not at all excited about using thalidomide.
gutsandgrowth 