Dr. Joseph D. Feuerstein, gastroenterologist at Beth Israel Deaconess Medical Center in Boston… “It’s rising in incidence and prevalence throughout the world,” he said, and gastroenterologists are still trying to figure out why it shows up when it does in different people.
Crohn’s disease was first described in 1932 by Dr. Burrill B. Crohn…
Prompt diagnosis and appropriate therapy to suppress inflammation in the digestive tract are extremely important because a delay can result in scar tissue and strictures that are not reversed by medication…
Crohn’s is not curable and most patients have to stay on medication indefinitely. That can create yet another stumbling block. The biologics are very costly…
This was a retrospective cohort study which included 169 patients who never smoked actively, 91 patients (54%) were exposed to passive smoking.
Exposed patients were more likely to undergo intestinal surgery than nonexposed patients (67% vs 30%; P < 0.001). Multivariate Cox regression analysis revealed that passive smoking was an independent risk factor for intestinal surgeries (hazard ratio, 1.7; 95% CI, 1.04–2.9; P = 0.034)
Smoking has long been identified as one of the strongest environmental risk factors for both the development of Crohn disease (CD) and the worsening of the disease course.
Studies in smokers with CD have reported that the risk of flares and complications matches that of nonsmokers with CD after 1 year of abstinence.
It would be reasonable to expect that a similar risk reduction exists for patients who can become passive-smoke-free. In addition, their likelihood of remaining smoke-free themselves is increased if they live in a smoke-free household.
My take (from editorial): “Clinicians should consider widening the scope of smoking cessation counseling to include not just patients but also their cohabitants.”
A recent review (JT Chang. NEJM 2020; 383: 2652-2664. Pathophysiology of Inflammatory Bowel Diseases) provides an in-depth description of the pathophysiology of inflammatory bowel disease (IBD). Digesting the article is akin to putting together a 1000 piece puzzle due to the complex interactions.
Some of the Key Points:
Based on genomewide association studies, there are “more than 240 risk variants that affect intracellular pathways recognizing microbial products (eg. NOD2); the autophagy pathway, which facilitates recycling intracellular organelles and removal of intracellular microorganisms (eg. ATG16L1); genes regulating epithelial barrier function (eg. ECM1); and pathways regulating innate and adaptive immunity (eg. IL23R and IL10).”
In this article, Figure 1 and 2 describe the intestinal mucosal immune system in health and disease. At baseline, this system promotes an antiinflammatory state “by virtue of active down-regulation of immune responses. For example, unlike macrophages in other parts of the body, intestinal macrophages do not produce inflammatory cytokines” after exposure to bacteria.
Dysbiosis is present with IBD; however, studies have been “unable to infer causal relationships.”
Germ-free mice, when given fecal material from patients with IBD have increased susceptibility to colitis as compared to those who received fecal material from a healthy person.
Thus, this leads to potential for mitigating intestinal inflammation by modulation of the microbiome.
However, the authors note that humans are colonized by trillions of viral, fungal, bacterial, and eukaryotic microbes.
Other components of IBD pathophysiology: reduced mucus layer, increased microbial adherence, dysregulation of tight junctions/increased permeability, dysfunctional Paneth cells, TNF, IL23, IL12, IL6, IL 17A, IL17F, IL22, Interferon-gamma, integrins, JAK inhibitors, T-cells
My take: This article is a useful reference detailing the complexity of IBD pathophysiology and tries to summarize a whole textbook of information into 12 pages.
“We found histologic evidence of UC activity (Geboes score ≥ 2B.1) in biopsies from 182 patients (65%) and endoscopic evidence of UC activity in 149 patients (53%) (substantial agreement, κ = 0.60).”
“Histologic features of UC activity were associated with increased rates of systemic corticosteroid use, colectomy, and hospitalization in the entire cohort (P < .05 for all) and associated with increased rates of systemic corticosteroid use in an analysis limited to patients in endoscopic remission (P < .001).”
At ileo-colonoscopy, 63% of patients had endoscopic healing and 55% had histologic evidence of healing. The level of agreement between endoscopic and histologic activity was fair (62%, K = 0.2250, P = .0064)
On multivariate analysis, only histologic healing was associated with decreased risk of clinical relapse (hazard ratio [HR], 2.05; 95% CI, 1.07–3.94; P = .031), medication escalation (HR, 2.17; 95% CI, 1.2–3.96; P = .011), and corticosteroid use (HR, 2.44; 95% CI, 1.17–5.09; P = .018).
D Kevans et al. Inflamm Bowel Dis 2020; 26: 1722-1729. Histological Markers of Clinical Relapse in Endoscopically Quiescent Ulcerative Colitis Key finding: In endoscopically quiescent UC (n=76), active histological inflammation …[is] adjunctive histological marker associated with increased likelihood of disease relapse. The associated editorial (1730-32 by Asher Kornbluth) quotes Voltaire: “A wise Italian says that the best is the enemy of the good.” He notes that there is “a very real risk of abandoning an effective drug while chasing the goal of some yet to be universally defined histologic remission.” Currently organizational guidelines (ACG, AGA, ECCO, IOIBD) do NOT suggest the use of histologic normalization as an endpoint at this point.
My take: These studies show that histologic healing in ileal Crohn’s disease and in ulcerative colitis are associated with better outcomes that endoscopic appearance. However, there are a lot questions because many patients, possibly a majority, will not achieve histologic healing despite aggressive treatment. Related technical issues include how many biopsies are needed to assess histology and having a validated histologic assessment.
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.
Lower intestinal barrier function is associated with increased risk for development of Crohn’s disease
More greenspace associated with lower rates of development of IBD
Exome sequencing has shown ~3% of pIBD with genetic mutations linked to monogenetic IBD & 1% with mutations which could benefit from HSCT. Identifying specific defects may lead to other treatments as well (eg. Leflunomide for TTC7A deficiency). Related blog posts:
Methods: “We conducted a national, prospective multi-centre IBD inception cohort study, including 1399 children. Diagnostic delay was defined as time from symptom onset to diagnosis >75 th percentile.”
In CD, diagnostic delay was associated with a 2.5-times higher rate of strictures/internal fistulae (HR 2.53, 95% CI 1.41-4.56)
Every additional month of diagnostic delay was associated with a decrease in height-for-age z-score of 0.13 standard deviations
Diagnostic delay was more common in CD, particularly small bowel CD
My take: Delays in diagnosis in this study were associated with stricturing/internal fistulising complications and growth impairment in paediatric CD. It is likely that inadequate treatment would increase the risk of these problems as well.
“In this largest genetic study of CC to date with histologically confirmed diagnosis, we strongly implicated the HLA locus and proposed potential non-HLA mechanisms in disease pathogenesis. We also detected a shared genetic risk between CC, celiac disease, CD, and UC.”
Anastomotic ulcers were present in 95 (52.2%) subjects. No factors were associated with anastomotic ulcer development.
Anastomotic ulcers were associated with disease recurrence (adjusted hazard ratio [aHR] 3.64)
The associated editorial by Philllip Fleshner (pg 1059) identifies are a number of methodologic flaws, noting that less than 20% of all ileocolonic resections were included and marked variability in postoperative assessment (from 29 days to 2897 days).
My take: (borrowed from the editorial) the “findings should convince us that anastomotic ulcers do not represent ischemic changes but are rather a reflection of disease progression.” Prospective studies with standardized surveillance would be helpful.