Anemia in IBD -NASPGHAN Position Paper

A Goyal et al. JPGN 2020; 71: 563-582 Full text (free). Anemia in Children With Inflammatory Bowel Disease: A Position Paper by the IBD Committee of the North American Society of Pediatric Gastroenterology, Hepatology and Nutrition.

Main Types of Anemia in Inflammatory Bowel Disease:

  • “IDA is the most common cause of anemia in children with IBD. True iron deficiency results from a number of factors, including chronic blood loss secondary to gastrointestinal bleeding, decreased iron absorption because of tissue or systemic inflammation and from reduced absorptive surface area. “
  • “Functional iron deficiency (FID) results from high levels of circulating hepcidin, which binds to and disables the iron transporter, ferroportin. Under the influence of hepcidin, ferroportin-mediated export of intracellular iron is stalled, leaving the iron trapped within the enterocytes and macrophages… the underlying inflammation, which induces hepcidin production can result in anemia secondary to FID.”
  • Anemia of chronic disease (ACD) “occurs from various downstream pathways secondary to inflammation.”

Table 4:

Recommended Testing

  • Screening Tests: “initially a complete blood count (CBC), CRP, and ferritin levels should be performed. If a patient is found to be anemic, then testing should include CBC with differential, including mean corpuscular volume (MCV), mean corpuscular Hgb concentration (MCHC), red cell distribution width (RDW), reticulocyte count, CRP, serum ferritin, and transferrin saturation (TSAT)”
  • Serum iron level … is … unreliable in the assessment of iron deficiency as the level fluctuates with several variables.
  • Transferrin saturation (TSAT) is a measure of the iron content in the circulating transferrin and reflects the availability of utilizable iron

Treatment of Anemia

  • In mild anemia (Hgb ≥10 g/dL) and/or quiescent disease, oral iron should be tried first.
  • Parenteral iron is indicated when oral iron is ineffective or poorly tolerated, in patients with moderate-severe anemia and/or with active inflammation.
  •  According to ECCO guidelines, an IV replacement goal of achieving of ferritin level of up to 400 μg/L is more likely to prevent recurrence of anemia…a transferrin saturation of 50% and serum ferritin of 800 μg/L should not be exceeded
  • Regarding iron effects on microbiome: studies indicate that dysbiosis at baseline worsens the unfavorable shifts in microbiome with oral iron therapy…Our position, however, is that further studies are required in humans before any reliable conclusions can be drawn. [My question: have the effects of oral iron supplementation on the microbiome been compared to IV iron supplementation on the microbiome?]
  • Table 6 lists various iron products including costs and dosing.
  • The hypersensitivity reactions to parenteral iron are mostly secondary to iron nanoparticles that trigger complement activation-related pseudo-allergy (CARPA)….It is important that parenteral iron be administered by trained personnel. Emergency medications and resuscitative equipment should be available during these infusions.

My take: This is a useful resource for a very common problem.

Related blog posts:

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

More Evidence That A Proinflammatory Diet May Increase the Risk of Crohn’s Disease

C-H Lo et al. Gastroenterol 2020; 159: 873-883. Full Text Link Dietary Inflammatory Potential and Risk of Crohn’s Disease and Ulcerative Colitis

The authors used Empirical dietary inflammatory pattern (EDIP) scores which were calculated based on the weighted sums of 18 food groups obtained via food frequency questionnaires. n=166,903 women and 41,931 men 

Key findings:

  • “In an analysis of 3 large prospective cohorts, we found dietary patterns with high inflammatory potential to be associated with increased risk of CD but not UC.”
    • Compared with participants in the lowest quartile of cumulative average EDIP score, those in the highest quartile (highest dietary inflammatory potential) had a 51% higher risk of CD (HR 1.51; 95% CI 1.10–2.07; Ptrend = .01).
  • There were 328 cases of CD and 428 cases of UC over 4,949,938 person-years of follow-up. The median age at IBD diagnosis was 55 years (range 29–85 years)

Discussion points:

  •  Food groups that are associated with unfavorable EDIP scores “are characterized by calorie-dense foods high in animal proteins, saturated fats, and glycemic carbohydrates, such as red meat, refined grain, and high-energy soft drinks.”
    • “Dietary patterns resembling the Western diet, characterized by higher intake of red meat, high-fat dairy, and refined grains, have been proposed to trigger the onset of intestinal inflammation by inducing changes in gut microbiome, altering host homeostasis, and regulating T-cell immune response.”
  • “In contrast, diets rich in fruit, vegetables, legumes, whole grains, fish, and poultry, resembling a more prudent and Mediterranean dietary pattern with high fiber and marine ω-3 content, may have anti-inflammatory effects.”

Related blog posts:

PPD (TB Skin Test) or Interferon-Gamma Release Assay (TB Blood Test)?

A recent editorial (JG Hashash et al. Inflamm Bowel Dis 2020; 26: 1315-1318Approach to Latent Tuberculosis Infection Screening Before Biologic Therapy in IBD Patients: PPD or IGRA?) provides some guidance on screening for tuberculosis prior to biologic therapy as well as background on how these tests work.

Key points:

  • The authors state that both a PPD or TB Blood Test (aka Quantiferon-TB Gold) are reasonable for most individuals, though they have a preference for the TB Blood Test.
  • For those with history of BCG vaccination, the TB Blood Test is recommended
  • Steroids are associated with negative PPD and indeterminate TB Blood Test.
  • The authors advocate baseline testing prior to biologic therapy for everyone.
  • Annual testing: For  those in high TB endemic areas, “we propose yearly chest x-ray in addition to IGRA [TB Blood Test]…in low endemic areas…we do not perform yearly chest x-rays nor do we check yearly IGRA unless mandated by a patient’s insurance.”

My take: TB blood testing is more convenient but more costly.  The authors indicate that  for patients from low endemic areas, yearly TB testing is mainly to check boxes mandated by insurance companies rather than improving care.

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

Outcomes Associated with Delayed Diagnosis in Pediatric Crohn’s Disease

A Ricciuto et al. Journal of Crohn’s and Colitis; 2020. jjaa197, https://doi.org/10.1093/ecco-jcc/jjaa197 Link: Diagnostic Delay Is Associated with Complicated Disease and Growth Impairment in Paediatric Crohn’s Disease

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.”

Key findings:

  • 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.

Related blog posts:

IBD Briefs -October 2020

EV Loftus et al.  AP&T  2020; 52: 1343-1365. Full text: Long‐term safety of vedolizumab for inflammatory bowel disease

GEMINI long‐term safety (LTS) study results –initiated 2009:

  • Enrolled patients (UC, n = 894; CD, n = 1349) received vedolizumab 300 mg IV every 4 weeks. Total of 7999 patient years of vedolizumab exposure.
  • Vedolizumab discontinuation due to AEs occurred in 15% (UC) and 17% (CD) of patients.
  • There were no new trends for infections, malignancies, infusion‐related reactions, or hepatic events, and no cases of progressive multifocal leukoencephalopathy
  • Conclusion from authors: “The safety profile of vedolizumab remains favourable with no unexpected or new safety concerns.”

Related blog posts:

AS Faye et al. Inflamm Bowel Dis 2020; 26: 1368-1376. Fertility Impact of Initial Operation Type for Female Ulcerative Colitis Patients (link includes video abstract)

Surgical options include Ileal pouch–anal anastomosis (IPAA), rectal-sparing colectomy with end ileostomy (RCEI), and ileorectal anastomosis (IRA). Conclusions based on “a patient-level state transition microsimulation in TreeAge Pro:”… “Despite an increased risk of infertility, our model results suggest that IPAA may be the optimal surgical strategy for female UC patients aged 20–30 years who desire children. For patients aged 35 years, RCEI should additionally be considered, as QALYs for RCEI and IPAA were similar.”   In older age group, RCEI’s increase rate of childbirth (28%), decrease time to childbirth (14 months) and 77% reduction in IVF are important factors.

Related blog posts:

R Tariq et al. Inflamm Bowel Dis 2020; 26: 1415-1422. Efficacy of Fecal Microbiota Transplantation for Recurrent C. Difficile Infection in Inflammatory Bowel Disease

In this retrospective study with 145 patients,  the overall cure rate of CDI after FMT was 80.0%, without CDI recurrence at median follow-up of 9.3 (range, 0.1–51) months. The authors concluded that “fecal microbiota transplantation effectively treats recurrent CDI in IBD patients but has no apparent beneficial effect on the IBD course.”

Related blog posts:

Isle of Palms (July 2020)

 

What’s Missing In Pediatric IBD Care

A recent single-site cross-sectional survey (HK Michel et al. J Pediatr 2020; 224: 94-101. Gaps Exist in the Comprehensive Care of Children with Inflammatory Bowel Diseases) of parents (n=161) and adolescents(n=84)  identified gaps in the comprehensive care of pediatric patients with inflammatory bowel disease (IBD).

Key points:

  • Discussions about family/peer relationships, school/extracurricular activities, and mood were not addressed in 30%-40% of participants.
  • Adolescents frequently reported that no one had talked to them about substance use (40%), sexual health (50%), or body image (60%)
  • 75% of adolescents and 76% of their parents reported that no one had discussed transitioning to an adult provider.

There is likely a wide variability in addressing psychosocial issues among providers and centers.  Limitations for this type of study includes recall bias and selection bias.

The associated editorial (MJ Ladinsky, MB Cohen, pg 20-22) urge us to ‘Mind the Gap.’  This likely means allowing sufficient time and arranging opportunities for teens to speak directly (& alone) with care provider.  Like other aspects of care, establishing a standardized approach is likely to be helpful.

My take: As noted on this blog previously, emotional health issues are likely more important than other aspects of IBD care that attract more consistent attention (eg. vaccination); the message is clear that these needs need to be addressed.

Related blog posts:

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

Published IBD-COVID-19 Data from SECURE-IBD & Others

When I received an email in EARLY MARCH of this year regarding SECURE-IBD, I thought the researchers were insightful and proactive.  Recently, the authors published their early findings: EJ Brenner, RC Ungaro et al. Gastroenterol 2020; 159: 481-491. Full Text PDF: Corticosteroids, But Not TNF Antagonists, Are Associated With Adverse COVID-19 Outcomes in Patients With Inflammatory Bowel Diseases: Results From an International Registry

“Surveillance Epidemiology of Coronavirus Under Research Exclusion for Inflammatory Bowel Disease (SECURE-IBD) is a large, international registry created to monitor outcomes of patients with IBD with confirmed COVID-19.”

Key findings:

  • 525 cases from 33 countries were reported (median age 43 years, 53% men)
  • Risk factors for severe COVID-19 among patients with IBD included increasing age (adjusted odds ratio [aOR], 1.04; 95% CI, 1.01–1.02), ≥2 comorbidities (aOR, 2.9; 95% CI, 1.1–7.8), systemic corticosteroids (aOR, 6.9; 95% CI, 2.3–20.5), and sulfasalazine or 5-aminosalicylate use (aOR, 3.1; 95% CI, 1.3–7.7).
  • Tumor necrosis factor antagonist treatment was not associated with severe COVID-19 (aOR, 0.9; 95% CI, 0.4–2.2)

Other COVID-19 articles from same journal:

My take: There is a tremendous amount of information regarding SARS-CoV-2 & COVID-19 with regard to the GI tract and liver disease.  For the most part, the data indicate that individuals need to continue to treat their underlying disease and that most therapies do not increase the risk of worsening infection; the biggest risk factors remain increasing age and common comorbidities (eg. obesity, hypertension, and diabetes).  The published studies also provide insight and recommendations for preventing SARS-CoV-2 for health care providers.

Related blog posts:

Crohn’s Disease Anastomotic Ulcerations

A recent retrospective study (RP Hirten et al. Inflamm Bowel Dis 2020; 26: 1050-1058Anastomotic Ulcers After Ileocolic Resection for Crohn’s Disease Are Common and Predict Recurrence) showed that anastomotic ulcers occur in over half of Crohn’s disease patients after ileocolic resection and are associated with Crohn’s disease recurrence and are persistent.

Key findings:

  • 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.

 

“Positioning Biologic Therapies in the Management of Pediatric Inflammatory Bowel Disease” & 14% of U.S. Infected with COVID-19

J Breton et al. Gastroenterology & Hepatology 2020; 16: 400-14. Full text: Positioning Biologic Therapies in the Management of Pediatric Inflammatory Bowel Disease

This is a terrific summary of biologic therapies for pediatric inflammatory bowel disease. Compared to adults, the pediatric data is much more limited.  This may affect recommendations.  For example, recent AGA guidelines for moderate to severe ulcerative colitis in adults suggests that either ustekinumab or tofacitinib is generally preferable as a 2nd line agent rather than vedolizumab in patients with primary infliximab failure (Blog post: AGA Guidelines: Moderate to Severe Ulcerative Colitis).  In the chart below, vedolizumab is recognized as a preferred 2nd line agent.

In the section on vedolizumab:

The favorable risk-benefit profile makes vedolizumab an ideal therapeutic choice for pediatric IBD. However, an important limitation is its delayed onset of action, for which corticosteroid use as bridge therapy is often necessary in this population that is already at increased risk of growth failure and bone loss. Recently, Hamel and colleagues published their small, single-center experience of using concomitant tacrolimus between anti-TNFα withdrawal to vedolizumab maintenance as a corticosteroid-sparing bridge therapy in moderate to severe IBD (Ref: Hamel B, Wu M, Hamel EO, Bass DM, Park KT. Outcome of tacrolimus and vedolizumab after corticosteroid and anti-TNF failure in paediatric severe colitis. BMJ Open Gastroenterol. 2018;5(1):e000195).

This article addresses therapeutic drug monitoring:

TDM is a key component of managing IBD patients on anti-TNFα therapy. While  reactive TDM of antiTNFα agents has been adopted by societal guidelines, there is an increasing body of literature to support the benefit of proactive TDM, particularly in pediatric populations

Conclusions from authors: Anti-TNFα agents have revolutionized the management of IBD, positively modifying the natural disease history in children. Importantly, inception cohort studies of pediatric CD and UC (RISK and PROTECT, respectively) have highlighted the variable course of disease and necessity of adopting an individualized approach with early use of biologic therapy in patients at risk of severe disease progression. 

Biologics Used in Pediatric Inflammatory Bowel Disease

Related blog posts:

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

 

IBD Update -September 2020

EM Kim et al. Inflamm Bowel Dis 2020; 26: 1232-38. Mucosal Eosinophilia Is an Independent Predictor of Vedolizumab Efficacy in Inflammatory Bowel Diseases n=65 patients. In IBD cohort, colonic eosinophilia (340 +/- 156 vs 236 +/- 124) was associated with clinical non-response to vedolizumab (as was prior anti-TNF treatment). In those with ulcerative colitis, mean eosinophil count was 438 in nonresponders compared to 299 in responders. In those with Crohn’s disease, colonic biopsies showed a non-significant increase in eosinophil count in non-responders compared to responders: 352 vs. 232.

MA Sofia et al. Inflamm Bowel Dis 2020; 26: 1251-9. Poor Sleep Quality in Crohn’s Disease Is Associated With Disease Activity and Risk for Hospitalization or Surgery

  • Ninety-two CD and 82 control subjects
  • Crohn’s disease subjects with Pittsburgh Sleep Quality Index (PSQI) >5 more often had inflammatory phenotypes and reported increased benzodiazepine and psychiatric medication use. Crohn’s disease subjects with PSQI >5 also reported more night awakenings due to pain and bathroom use.
  • The PSQI correlated with HBI
  • PSQI >8 was predictive of surgery or hospitalization (hazards ratio 5.37; 95% confidence interval, 1.39-27.54).

My take: This study indicates that poor sleep is a marker for increased adverse outcomes/disease activity.  It may be that sleep disturbance is due to increased disease activity or this may be a bidirectional issue in which poor sleep triggers more disease activity as well.

A Ricciuto et al. Clin Gastroenterol Hepatol 2020; 18: 1509-1517. Primary Sclerosing Cholangitis in Children With Inflammatory Bowel Diseases Is Associated With Milder Clinical Activity But More Frequent Subclinical Inflammation and Growth Impairment

This retrospective study provides additional information on the observation that children with PSC often have subclinical disease; it is similar to a prospective study by the same group in 2018 (n=37):  (prior blog post: Active Colitis More Likely in Children in Clinical Remission Who Have IBD and PSC) Key finding: Higher proportions of children with PSC-IBD had backwash ileitis, pancolitis, and rectal sparing, and more severe right-sided disease, than controls (P < .05). Conclusions: “Despite the mild clinical activity of IBD in patients with PSC, lack of symptoms does not always indicate lack of mucosal inflammation. Children with PSC-IBD have greater growth impairments compared with children with ulcerative colitis or IBD-unclassified.”