Transient Exocrine Pancreatic Insufficiency or Misleading Tests?

A recent retrospective study (J Garah et al. JPGN 2019; 68: 574-77) showed that many cases of exocrine pancreatic insufficiency, based on a low fecal elastase (<200), resolved over ~6 months.

Background:

  • 17 of 43 children had adequate data and no other recognized comorbidities which could explain low elastase levels
  • In these 17 children the median age was 3 years
  • Presenting symptoms were failure to thrive, or diarrhea. Children with known etiologies (eg. cystic fibrosis, Shwachman-Diamond, cholestatic liver disease) were excluded.
  • Median elastase at time of diagnosis was 71

Key findings:

  • Median time for normalization of elastase was 6 months. Patients received pancreatic supplements until elastase normalized.
  • 11 of the 17 had values of elastase <100, and an additional two had values of 105.
  • In all 17 children without identifiable underlying diseases, the pancreatic insufficiency was transient.
  • Only two children had fat soluble vitamin deficiency associated with pancreatic insufficiency

The article discusses the use of elastase for diagnosis of pancreatic insufficiency in comparison to more direct/invasive testing which can be difficult to perform.  It is important to recognize that elastase values are often unreliable in the presence of diarrhea or if diluted by urine.  Repeated assays may be needed to have confidence that elastase

My take: This report identifies “transient pancreatic insufficiency” as a frequent explanation for many children and may represent a postinfectious etiology. Thus, if no comorbidity is identified, the prognosis is favorable in most children.

Sculptured Cypress Trees in Retiro Park, Madrid

Bad Diets –>High Mortality

A recent article in Lancet (“Health effects of dietary risks in 195 countries, 1990–2017:
a systematic analysis for the Global Burden of Disease Study 2017″ -open access) estimated that bad diets lead to 11 million deaths per year. Thanks to Ana Ramirez for sending me this article. “High intake of sodium, low intake of whole grains, and low intake of fruits were the leading dietary risk factors for deaths and DALYs globally and in many countries.”

A summary of this study was reported on NPR: Bad Diets Are Responsible For More Deaths Than Smoking, Global Study Finds

An excerpt:

About 11 million deaths a year are linked to poor diet around the globe…

As part of a new study published in The Lancet, researchers analyzed the diets of people in 195 countries using survey data, as well as sales data and household expenditure data. Then they estimated the impact of poor diets on the risk of death from diseases including heart disease, certain cancers and diabetes. (They also calculated the number of deaths related to other risk factors, such as smoking and drug use, at the global level.)…

“Generally, the countries that have a diet close to the Mediterranean diet, which has higher intake of fruits, vegetables, nuts and healthy oils [including olive oil and omega-3 fatty acids from fish] are the countries where we see the lowest number of [diet-related] deaths,” …

What would happen if everyone around the globe began to eat a healthy diet, filling three-fourths of their plates with fruits, vegetables and whole grains? We’d run out…

Improving diets won’t be easy: A range of initiatives may be needed, including nutrition education and increased access to healthy foods, as well as rethinking agricultural production.

Related blog posts:

 

IBD Update April 2019

Briefly noted:

Link (from KT Park’s twitter feed): What New Treatments for Crohn’s disease and Ulcerative Colitis Are Being Developed?

R Wittig et al. JPGN 2019; 68: 244-50. This study from Germany, using health insurance data, identified an overall pediatric inflammatory bowel disease (IBD) incidence of 17.41 per 100,000 in 2012 compared to 13.65/100,000 in 2009.  This is one of the highest incidence rates reported and agrees with other data suggesting increasing rates of IBD in pediatric populations.

B Christensen et al. Clin Gastroenterol Hepatol 2019; 17: 486-93.  This study provides data from 20 patients (CD =9, UC =11) who were treated with a combination of a calcineurin inhibitor and vedolizumab.  The calcineurin inhibitor was used as a ‘bridge’ treatment until the slower acting vedolizumab could be effective. After 52 weeks of treatment, 33% of the CD patients and 45% of the UC patients were in steroid-free clinical remission.  Three serious adverse events associated with calcineurin treatment.

G Pellet et al. Clin Gastroenterol Hepatol 2019; 17: 494-501. Retrospective study of calcineurin inhibitor induction with vedolizumab in 39 patients with refractory ulcerative colitis (36 had failed anti-TNF Rx).  11 patients (28%) required colectomy. week 14 response and remission noted in 56% and 38% respectively. Four serious adverse events were observed.

N Nalagatla et al. Clin Gastroenterol Hepatol 2019; 17: 494-501. In a retrospective study of 213 patients with steroid refractory acute severe ulcerative colitis, the authors did not find lower rates of colectomy in patients who received an accelerated infliximab dosing.  However, they were unable to control for confounding by disease severity. Patients who received an intial dose of 10 mg/kg had a lower colectomy rate than patients who received an initial dose of 5 mg/kg. Colectomy rates for accelerated vs standard infliximab dosing –in-hospital: 9% vs 8% respectively, at 3 months: 20% vs 14% respectively, at 12 months: 28% vs 27% respectively.

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Shenandoah National Park

Celiac Hepatopathy 2019

A recent retrospective study (E Benelli et al. JPGN 2019; 68: 547-51) examines a large cohort of patients (=700) who were diagnosed with celiac disease (CD) from 2010-2016 and had available liver transaminases.

Key findings:

  • ALT values >40 U/L were elevated in only 3.9% (27/700)
  • Younger age (<4.27 years) correlated with a higher risk of liver involvement with OR 3.73
  • Of these 27 patients with elevated ALT, 18 had adequate followup.  All but 3 patients normalized ALT values after at least 1 year; of these, 1 was diagnosed with sclerosing cholangitis. In the other two, one was thought to be nonadherent with gluten-free diet and one had dropped ALT to 47 U/L.
  • Thus, definitive autoimmune liver disease was identified in only one patient

My take: This study shows a lower rate of liver involvement than previous studies.

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Joshua Tree National Park

 

ESPGHAN Peutz-Jeghers Syndrome Position Paper

Management of Peutz-Jeghers Syndrome in Children and Adolescents: A Position Paper by the ESPGHAN Polyposis Working Group; Link:JPGN 2019; 68 (3): 442-452

This position paper serves as a good review and makes clear recommendations for evaluation and management.

In a single individual, a clinical diagnosis of PJS may be made when any one of the following is present:
1. Two or more histologically confirmed PJS polyps
2. Any number of PJS polyps detected in 1 individual who has a family history of PJS in close relative(s)
3. Characteristic mucocutaneous pigmentation in an individual who has a family history of PJS in close relative(s)
4. Any number of PJS polyps in an individual who also has characteristic mucocutaneous pigmentation.

SUMMARY OF RECOMMENDATIONS

  • Recommendation 1 Predictive genetic testing for an asymptomatic at risk child should be offered from the age of 3 years and should be performed earlier in a symptomatic at-risk child. (moderate recommendation, low-quality evidence, agreement 90%)
  • Recommendation 2 Lip and mucosal freckling is not diagnostic of PJS alone. Patients with lip and mucosal freckling suggestive of PJS should be referred to a geneticist for diagnostic genetic testing. Investigation of the GI tract is recommended to start no later than age 8 unless symptoms arise earlier. (weak recommendation, low-quality evidence, agreement 100%)
  • Recommendation 3 GI surveillance by upper GI endoscopy, colonoscopy, and VCE should commence no later than 8 years in an asymptomatic individual with PJS, and earlier if symptomatic…and generally be repeated every 3 years. Earlier investigation of the GI tract should be performed in symptomatic patients. (moderate recommendation, low-quality evidence, agreement 90%)
  • Recommendation 4 Patients with symptomatic intussusception should be urgently referred for surgical reduction. There is no role for radiological or endoscopic reduction of intussusception in a symptomatic child with intestinal obstruction from a PJS polyp. At laparotomy, patients should ideally undergo an intraoperative enteroscopy to clear the small bowel of other PJS polyps. (strong recommendation, low-quality evidence, agreement 100%)
  • Recommendation 5 Elective polypectomy should be performed to prevent
    polyp-related complications. Small bowel polyps >1.5 to 2 cm in size (or smaller if symptomatic) should be electively removed to prevent intussusception. Endoscopic, surgical, and combined approaches all have their merit and the choice of modality should be made on a case by case basis (weak recommendation, low-quality evidence, agreement 100%)
  • Recommendation 6 LCCSCTs [Large-cell calcifying Sertoli cell tumours of the testes] leading to feminizing manifestations including gynaecomastia are associated with the PJS and males should be assessed for this at clinical assessment.
  • Recommendation 7 There is no role for pharmacological agents as a treatment or for chemoprevention in PJS. (strong recommendation, low-quality evidence, agreement 100%)
  • Recommendation 8 Cancer in children with PJS is an extremely rare event. Children and adolescents should be routinely clinically examined for features of sex cord tumours

Related blog posts:

Near Chattahoochee River

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

Getting the Most Out of Vedolizumab

A recent cross-sectional study (B Al-Bawardy et al. Inflamm Bowel Dis 2019; 25: 580-6) correlated vedolizumab (VDZ) trough drug levels (VDT) and clinical outcomes in 171 patients (62% Crohn’s disease (CD), 31% ulcerative colitis (UC), and 7% indeterminate colitis (IC)).

Key findings:

  • Median VDT was 15.3 microgr/mL.
  • Median VDT was 17.3 microgr/mL for patients with normal CRP compared with 10.7 for patients with high CRP.  This differnece was noted significantly for CD (20.3 vs 10.4) but not for UC.
  • No relationship  between VDT and mucosal healing was noted.
  • Shorter dose intervals and lower BMO resulted in higher VTLs
  • Only 1 patient had detectable antibodies to VDZ

A second systematic review (L Peyrin-Biroulet et al. Clin Gastroenterol Hepatol 2019; 17: 838-46) analyzed data from 10 cohorts who had received vedolizumab.  Most had prior anti-TNF exposure. Key finding: the pooled incidence rates of loss of response were 47.9 per 100 person-years of follow up among patients with CD and 39.8 per 100 person-years of follow up among patinets with UC.  Dose intensification restored response to the drug in 53.8% of secondary non-responders.

My take: While VDZ dose intensification can restore response, the utility of therapeutic drug monitoring is unclear with VDZ therapy.

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ESPGHAN Juvenile Polyposis Syndrome in Children –Position Paper

Management of Juvenile Polyposis Syndromes in Children and Adolescents: A Position Paper from the ESPGHAN Polyposis Working Group: Link: JPGN 2019; 68 (3): 453-462

Diagnosis: JPS is diagnosed by use of the following criteria in the absence of  extraintestinal features consistent with PHTS (Cowden syndrome [CS] or Bannayan-Riley-Ruvalcaba syndrome) (6):
1. Five or more JPs of the colon or rectum, or
2. JPs in other parts of the GI tract, or
3. Any number of JPs and a positive family history.

SUMMARY OF SOME OF THE RECOMMENDATIONS
1. Routine predictive genetic testing for paediatric patients at risk of developing JPS should start at 12 to 15 years of age. Children that develop rectal bleeding earlier than this age should undergo colonoscopy and then proceed to genetic testing if polyps are identified. Weak recommendation, very low quality of evidence.
2. Colonoscopic surveillance should commence from age 12 to 15 years, or earlier if symptomatic. Once polyps (>10 mm) are detected they should be removed and olonoscopy repeated annually until polyps >10 mm have been resected, then
repeated every 1 to 5 years. Weak recommendation, very low quality of evidence.
3. Surveillance of the upper GI tract in affected or at-risk JPS patients is not required in childhood or teenage years, unless there is unexplained anaemia or upper GI symptoms. Weak recommendation, very low quality of evidence.
4. Paediatric patients with SMAD4 mutation should be evaluated for HHT including screening and preventative treatment for cerebral and pulmonary AVMs. Weak recommendation, very low quality of evidence.
5. In JPS patients with an isolated BMPR1A gene mutation, there are no additional investigations required beyond the endoscopic procedures described above. Children with BMPR1A mutation and early onset polyposis and/or a severe phenotype and/or
extraintestinal manifestations should be evaluated for PTEN mutation. Weak recommendation, very low quality of evidence.
6. In a child with a single JP, a repeat colonoscopy is not routinely required. Weak recommendation, very low quality of evidence.
7. If a specific gene mutation has been detected in a child, then genetic testing should be offered to all first-degree family members. If no specific gene mutation was detected, then first degree relatives should be referred for screening colonoscopy at the age of 12 to 15 years. Weak recommendation, very low quality of evidence.
8. There is no role for chemoprevention in JPS. Weak recommendation, very low quality of evidence.

Related blog postUpdated Guidelines on Genetic Testing/management for Hereditary GI Cancer Syndromes

Atlanta Zoo

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