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:

How Helpful is Endoscopic Pancreatic Testing in Pediatrics?

A recent study (P Hopson et al. JPGN 2019; 68: 854-60) reports a high rate of isolated amylase deficiency of 10.1% in their cohort. Is this really accurate? I am skeptical.

  • This is a retrospective study and the authors undertook endoscopic pancreatic function testing (ePFT) in a large number of patients, 712 over a 6 year period.  The authors state “whenever there is clinical indication for esophagogastroduodenoscopy (EGD) we usually obtain” ePFT collections.
  • To determine the amylase levels, the authors relied upon their in-house laboratory.  Before accepting widespread deficiencies in amylase production, it would be useful to have specimens checked in more than one laboratory. At the same time, given the normalcy of the other pancreatic enzymes, it is likely that the specimens were of good quality.
  • 59 of the 72 (82%) patients with isolated amylase deficiency were younger than 2 years. It is notable that in the same issue, some of the same authors in a review article describe the technique for ePFT (JPGN 2019; 68: 768-76) and note that amylase activity is undetectable at 1 month of age and is normal at 2 years of age.  “Data are lacking as to when it is expected that most children have normal pancreatic amylase activity before 2 years of age.”
  • The authors note that 48 patients (67%) with isolated amylase deficiency had failure to thrive or poor growth.

Amylase Levels:

  • Looking at the authors’ Figure 1, they do provide their mean amylase levels; they considered a level below 10.3 micromol/min/mL to be deficient.  Is this the right cutoff? Is there evidence that levels below this result in a disease state?
  • Particularly in the first year of life, the amylase activities are much lower: approximately 2 micromol/min/mL for age 0-6 months and 12 micromol/min/mL for 6-12 months.
  • In their cohort of 72 with abnormal amylase levels, 35 (approximately half) are less than 1 year of age.  Thus, given how low the mean levels are, it is not surprising that nearly half of the patients (35/82) in this age group had abnormal ePFT.
  • Even in the 1-1.5 year olds, the mean amylase activity is lower than the older group (approximately 24 micromol/min/mL compared to more than 40 micromol/min/mL for patients older than 6 years).  The authors found 25% of the ePFT testing in this age group (1-15. yr olds) to have isolated amylase deficiency; again, this seems implausible.
  • It is notable that there is not a control population.  How often in healthy patients less than 2 years of age is the amylase level below their cutoff? In fact, the authors state that 10 of their patients with isolated amylase deficiency had constipation, and 5 had reflux which would be quite atypical presenting indications.

The technique for obtaining ePFT is detailed in the review (JPGN 2019; 68: 768-76) and includes the following:

  • Before endoscopic intubation, “a bolus of secretin (0.2 mcg/kg to max of 16 mcg) is administered” (or alternatively synthetic CCK octapeptide in a dose of 0.02 or 0.04 mcg/kg).
  • Initial fluid in stomach and duodenum is aspirated and discarded
  • Using an aspiration catheter (or thru biopsy channel if scope too small), collect 3 to 4 aliquots of fluid between 3-10 minutes after injection of secretin (should be completed within 10 minutes of secretin)
  • Place immediately on ice or dry ice
  • Samples with low pH may be contaminated
  • Avoid trauma to mucosa as bleeding can give erroneous results

I would suggest a more selective approach in utilizing endoscopy to check for both pancreatic function as well as disaccharidases.  The sensitivity, specificity, positive predictive value and negative predictive value of a test is highly dependent on the study population. In those at low risk, the results of the testing is highly suspect.

My take: The reference to the review article is worth keeping as it gives a clear description of endoscopic pancreatic function testing.  The study describing a 10% rate of amylase deficiency among a large cohort of pediatric patients requires careful interpretation, particularly as more than 80% of the deficiency group were less than 2 years of age. Clearly, a prospective study is needed.  In those with possible isolated amylase deficiency at a young age (<2 years), a double-blind randomized trial may be needed to determine if enzyme supplementation is beneficial.

Related blog posts: Transient Exocrine Pancreatic Insufficiency or Misleading Tests?

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.

 

Camille Passaro, Rue Saint-Honore por la Tarde. Efecto de lluvia.  Thyssen-Bornemisza Museum; https://www.museothyssen.org/en/collection/artists/pissarro-camille/rue-saint-honore-afternoon-effect-rain

 

 

 

 

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)

Detergent Pod Ingestions -Is an Endoscopy Needed?

A recent study (A Singh et al. JPGN 2019; 68: 824-8) provides a descriptive retrospective review of a single center experience with detergent pods (a.k.a. laundry pods or dishwater pods). There is very little published in this area and no clear consensus on management.

For me, the most interesting finding in the study is the discrepancy between the ENT service which only did a direct laryngoscopy-bronchoscopy (DLB) in 6 of 23 (26%) ingestions compared with 21 of 23 (91%) EGD rate among patients who presented to the GI service.

Key findings:

  • Of those undergoing an EGD, 76% were normal; abnormal findings (edema, erythema or ulceration) were present in 24% (though figure 4 suggests erythema in 28%). Ulceration was noted in 14%.
  • In the DLB cohort (n=6), 33% were normal and 67% were abnormal.

Unfortunately, this report has a lot of limitations:

  • It did not provide any information regarding long-term effects (if any were present)
  • It did not provide much guidance in determining whether an EGD is worthwhile. The authors did note that patients with oral injuries were more likely to have an abnormal EGD. 80% of patients with positive oropharyngeal findings had an abnormal EGD compared with 20% with a normal oropharyngeal exam.
  • In the discussion, the authors reference a study which reported esophageal injury in only 0.1% of cases (Davis et al.  2016 May;137(5). pii: e20154529. doi: 10.1542/peds.2015-4529. Pediatric Exposures to Laundry and Dishwasher Detergents in the United States: 2013-2014). There were two deaths in this study.

My take: This would have been a good report to have an associated commentary/expert opinion.  Even if an EGD is abnormal, this does not mean that the EGD was needed.  The bigger question is how often an EGD would improve management.  Given the lack of specific treatments, it is likely that an EGD should be reserved for severe cases –which could include the following:

  • intentional ingestions
  • significant oropharyngeal burns
  • food refusal
  • drooling/difficulty managing secretions
  • stridor

Related blog post: New caustic danger from detergent pods

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.

Detergent Pods -Still an Issue -This Tweet is from June 5, 2019

William Meyers

Yesterday I attended the Inaugural William Meyers Lecture and intended for this post to be a summary of that.  Sadly, he passed away last night.

Billy, a partner in our GI group, had been fighting brain cancer for the past year. This lecture was established to honor him. Jose Garza gave a lecture which highlighted the important work of the neurogastroenterology service, established in large measure by Billy.

Also, Billy served on numerous hospital committees.  Much of his efforts were ‘behind the scenes’ and usually the type of work that many of us seek to avoid.  In addition to working on these hospital committees, Billy remained a busy clinician.  In the past year, I’ve had the opportunity to interact with many of his patients and families.  Uniformly I have heard how compassionate and patient he was, even with the most complex situations.  In the 22 years that I had the opportunity to work with Billy, I cannot seem to recall him ever being flustered.  He was a truly wonderful person, physician, and mentor..   I will miss his kindness and friendship.