How Often is Arthritis a Presenting Feature of Pediatric IBD & How to Make the Right Diagnosis

A recent retrospective study (R Levy et al. J Pediatr 2019; 209: 233-5) analyzed the musculoskeletal presenting manifestations of pediatric inflammatory bowel disease (IBD).

In their cohort of 715 patients with IBD, 137 had arthritis and/or arthralgia.  28 of these 137 patients (3.9% of total cohort) had arthritis preceding the diagnosis of IBD and were eligible for this study.  Only 23 had complete data and were compared with 46 children with arthritis due to JIA (n=21), FMF (n=7), and postinfectious arthritis (n=18).

Key findings:

  • Patients with subsequent IBD diagnosis were more likely to have sacroiliac involvement (34.8% vs. 2.2%), more likely to have anemia (mean hgb 10.5 vs 12), more likely to have low albumin (mean 3.5 vs 4.3) and to have higher inflammatory markers (ESR 81 vs 46; CRP 6.6 vs 4.5 mg/dL)
  • In patients with calprotectin levels, 5 of 6 were >300 mg/kg and one was borderline
  • On direct questioning at time of IBD diagnosis, prolonged gastrointestinal symptoms (e.g. abdominal pain, diarrhea, weight loss, aphthous ulcers) were evident in 78%.
  • 4 of the 23 (17.3%) were diagnosed with IBD during the primary investigation. Ultimately, Crohn’s diagnosis was established in 87% of the IBD group.

My take: This study is important for pediatricians and rheumatologists. ~4% of children presenting with arthritis have IBD.  Careful interrogation for GI symptoms (and perianal exam) will avoid diagnostic delay in most patients as would a stool calprotectin. Features like sacroileitis, and abnormal labs should also increase the suspicion for IBD.

Briefly noted: In a study discussing pediatrician beliefs about JIA (MR Pavo, J de Inocencio, J Pediatr 2019; 209: 236-9) there is an important caveat for GI doctors:

“It is clear that booster vaccinations against measles, mumps, rubella, or varicella zoster virus, can be considered in patients receiving < 15 mg/m-squared/week of MTX [methotrexate]”  (Pediatr Rheumatol Online J 2018; 16: 46).

Related blog post:

  • IBD Update Feb 2019 -last entry shows study indicating that patients with IBD and arthritis were more likely to require biologics.

Calprotectin:

El Retiro Park, Madrid

 

Early Life Events and the Development of Inflammatory Bowel Disease

Full Text via AGA Journal Link: Events Within the First Year of Life, but Not the Neonatal Period, Affect Risk for Later Development of Inflammatory Bowel Diseases

A recent study (CN Bernstein et al. Gastroenterol 2019; 156: 2190-7; editorial 2124) delves into the topic of early life risk factors for the development of IBD. In the background, the author note that in 2018, 267,983 Canadians (0.73%) were estimated to be living with IBD and there is a forecast that this will increase to 402,853 by 2030.

This study used a Manitoba database and examined the records of individuals diagnosed with between 1984-2010. In addition, they correlated this data with individual data of the postnatal period between 1970-2010. From this database, they analyzed 825 individuals with IBD and 5999 matched controls.

Key Findings:

  • The strongest risk factor for the development of IBD was a maternal diagnosis of IBD with an odds ratio (OR) of 4.53; the OR was higher for CD at 5.98 compared to OR of 2.71 for UC
  • Infections in the first year of life was associated with an OR of 3.06 for IBD diagnosed before age 10 years, and OR of 1.63 for IBD diagnosis before age 20 years.  Only infections in the first year of life were correlated with IBD as infections during the first 3 years of life were not associated with a significant increased risk.
  • While infections in the first year of life were associated with an increase risk of IBD, the authors could not demonstrate that individuals who developed IBD had more infections than unaffected sibling controls (though they did have more infections than the entire control cohort).
  • Highest socioeconomic quintile, also, had an increased OR of 1.35.
  • Gastrointestinal illnesses (like abdominal pain) were not found to be associated with the later development of IBD.

It is unclear whether infections in early life increase the risk of IBD or whether other factors like antibiotics contribute to the higher rate of IBD.  The authors did not find more immunodeficiency disorders in the IBD cohort compared to controls.

My take: This study identified genetic risk as substantially greater than specific environmental risks.  However, the increasing incidence of IBD suggests that environmental factors are quite significant, as genetic risk factors are less likely to change enough to account for the changes in epidemiology.  As such, there are a few explanations:

  1. There are other unidentified environment risk factors
  2. Some individuals are more susceptible to the changes that have occurred in the environment; that is, their environmental exposures are not significantly different from their peers but are significantly different than individuals from 20, 40, 60 and 100 years ago.

From AGA Journal link

Related blog posts:

Backwash Ileitis Plus One

Briefly Noted:

RM Najarian et al. JPGN 2019; 68: 835-40.  This retrospective study found microscopic/’backwash’ ileitis in 16% (17/105) of patients with new-onset ulcerative colitis. This occurred predominantly in patients with pancolitis (82%). The authors note that the term “backwash ileitis” was derived from an unproven hypothesis that the inflammation was related to retrograde contact with inflammatory substances, though some now consider ileal involvement as a secondary involvement “akin to the upper tract inflammation that can be seen in a subset of patients with UC.” The authors recommend that isolated histologic inflammation of the ileum should “not be construed as being diagnostic of either ‘indeterminant colitis’ or CD [Crohn’s disease].”

K van Hoeve et al. JPGN 2019; 68: 847-53. This retrospective study of 35 children found that higher infliximab levels during induction was associated with higher rates of clinical and biologic remission at 52 weeks. Groups at risk for lower troughs included patients with a lower weight and/or lower hemoglobin level.

Rafaela Flores Calderon by Antonio Maria Esquivel, Museo del Prado (Image in Public Domain)

Antidepressants for Patients with IBD and Their (Beneficial) Affect on Bowel Disease Activity

A recent population-based cohort study (MS Kristensen et al. Inflamm Bowel Dis 2019; 25: 886-93) indicates that antidepressants are likely to be beneficial for patients with inflammatory bowel disease and could lower disease activity in addition to improving mood.

This study population, n=42,890, with prospectively collected data comprised all patients in the Danish National Patient Registry from 2000-2017 with ICD diagnoses of ulcerative colitis (UC, 69.5%) or Crohn’s disease (CD, 30.5%).  Outcome measures included markers of disease relapse:

  • hospitalizations with IBD as primary diagnosis
  • surgery with IBD as primary operation code
  • step-up medications with corticosteroids or anti-TNF treatment

Key findings:

  • After adjusting for confounders, lower incidence rate of disease activity was found among antidepressant users than nonusers.
    • For CD, the incidence rate ratio was 0.75 (CI 0.68-0.82).
    • For UC, the incidence rate ratio was 0.90 (CI 0.84-0.95).
    • For CD patients without prior use of antidepressants before diagnosis of CD, there was markedly lower incidence rate ratio of 0.51 (CI 0.43-0.62).
  • 28% of the study population redeemed at least 1 prescription for an antidepressant at some point.  This is similar to a Finnish study in which antidepressant use in IBD was 28% compared to 19% in general population

The authors note that anti-depressants may affect the level of pro-inflammatory cytokines which are involved in the pathogenesis of IBD.  This study did not assess potential adverse effects of using anti-depressants.

My take: This study is intriguing and suggests that antidepressants may improve the disease course in IBD. Whether this is related to more favorable brain-gut interaction or whether this is related to drug effects on inflammatory agents is unclear.

Related blog post: Psychosocial Problems in Adolescents with IBD

Park Guell -Fantastic Park in Barcelona (need to buy a pass to get to some parts)

Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications/diets (along with potential adverse effects) should be confirmed by prescribing physician/nutritionist.  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.

 

Vedolizumab vs Adalimumab for Infliximab Failure in Ulcerative Colitis –Which is Better?

A recent retrospective study (A Favale et al. Comparative Efficacy of Vedolizumab and Adalimumab in Ulcerative Colitis Patients Previously Treated With Infliximab Inflammatory Bowel Diseases, izz057, https://doi.org/10.1093/ibd/izz057 Published: 01 April 2019) suggests that vedolizumab is more effective for ulcerative colitis with secondary infliximab failure.

Here’s the abstract:

Background

Adalimumab (ADA) and vedolizumab (VDZ) have shown efficacy in moderate to severe ulcerative colitis (UC) patients who failed infliximab (IFX). Although, a comparative efficacy evaluation of ADA and VDZ in this clinical setting is currently missing.

Aim

The aim of this study is to compare the efficacy of ADA and VDZ in patients affected by UC who failed IFX.

Methods

Clinical records of UC patients from 8 Italian IBD referral centers who failed IFX and were candidates to receive either ADA or VDZ were retrospectively reviewed. The primary end point was therapeutic failure at week 52. Secondary end points included therapy discontinuation at weeks 8, 24 and 52, the discontinuation-free survival, and safety.

Results

One hundred sixty-one UC patients, 15 (9.2%) primary, 83 (51.6%) secondary IFX failures, and 63 (39.2%) IFX intolerants were included. Sixty-four (40%) patients received ADA and 97 (60%) VDZ as second line therapy. At week 52, 37.5% and 28.9% of patients on ADA and VDZ, respectively, had therapeutic failure (P = 0.302). However, the failure rate was significantly higher in the ADA group as compared with VDZ group among IFX secondary failures (48.0% ADA vs 22.4%VDZ, P = 0.035). The therapy discontinuation-free survival was significantly higher in the group of IFX secondary failures who received VDZ as compared with ADA at both the univariate (P = 0.007) and multivariate survival analysis (OR 2.79; 95% CI, 1.23–6.34; P = 0.014). No difference in the failure and biologic discontinuation-free survival was observed in the IFX primary failure and intolerant subgroups.

Conclusion

Vedolizumab might be the therapy of choice in those UC patients who showed secondary failure to IFX.

Link to video abstract (2 min):  Comparative Efficacy of Vedolizumab and Adalimumab in Ulcerative Colitis Patients Previously Treated With Infliximab