Will NOTES come to pediatrics?

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Natural orifice translumenal endoscopic surgery (NOTES) has been receiving increasing attention and is being considered as a potential alternative to laparascopic surgery; but it will be a long time before NOTES comes to pediatrics.  Initial studies for several indications have been published in the last few years and this experience has recently been reviewed (Gastroenterology 2012; 142: 704-10).

Potential operations include the following:

  • Cholecystectomy.  This has been accomplished transgastric and transvaginally.  One multicenter study published experience with 362 transgastric cases and another with 551 transvaginal cases.
  • Thyroidectomy via a translingual approach.
  • Esophageal myotomy via a transesophageal approach.
  • Appendectomy via a transvaginal approach.
  • Rectal cancer resection via a transrectal approach.

Thus far, complications have been low & no deaths; only infrequently has a laparascopic or open procedure been needed to salvage the operation.  The main limitation to further use of NOTES has been adequate instrumentation and a critical mass of investigators to explore this technique.  As expertise develops in this area, a much larger number of procedures will be undertaken.  In many ways, NOTES is akin to laparascopy in its early days.  Potential advantages of decreased pain and faster recovery are the motivation to continue to work on NOTES.

CLMP–why some children are born with a short gut

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CLMP stands for Coxsackie- and adenovirus receptor-like membrane protein. It is required for intestinal development (Gastroenterology 2012; 142: 453-62).

In this study of seven patients from five families with congenital short-bowel syndrome (SBS), the authors identified a loss-of-function of CLMP in five of the patients.  CLMP is a tight-junction-associated protein that is expressed in the intestine of human embryos throughout development.

To study the effect of CLMP expression, the authors created a zebrafish model with compromised CLMP activity.  This lead to offspring with a foreshortened body and intestine, strengthening the evidence that CLMP dysfunction is responsible for congenital short-bowel syndrome.

Additional references/previous related posts:

MicroRNA signature for eosinophilic esophagitis

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In a previous post discussing MicroRNAs (miRNAs) (MicroRNAs and biliary atresia), I stated that “Despite this intriguing research, it not clear whether or when miRNAs will have an important role in bedside management.”  Well, as more articles emerge on miRNAs, it is becoming clear that miRNAs will have a role in clinical medicine; the questions are when and what cost.

The latest study (J Allergy Clin Immunol 2012; 129: 1064-75) by Lu et al from Cincinnati shows how this technique can identify a specific signature for eosinophilic esophagitis (EoE) and how miRNAs can serve as a biomarker for disease response.  The investigators took plasma and esophageal biopsy specimens from patients with EoE, reflux esophagitis, and healthy controls; they used an array comprising 677 miRNAs.  254 miRNAs were expressed at greater than background levels, but 21 upregulated miRNAs and 11 downregulated miRNAs were markedly different.

To quickly understand how useful this technology could become requires a glance at the “heat maps” showing the expression profile of the 21 upregulated miRNAs and the 11 downregulated miRNAs, comparing EoE with healthy controls (Figures 1 & 3).  In addition, in Figure 3, it is readily apparent that the expression pattern is completely different from reflux esophagitis.  Furthermore, this figure demonstrates visually a normal-appearing pattern in patients who respond to fluticasone.

Other figures in the article and in the appendix demonstrate the complex relationships between these specific miRNAs and target genes.

Key points:

  • miRNAs from tissue or blood could serve as biomarkers for the presence of EoE and response to therapy
  • Of the identified miRNAs, miR-21 and miR-223 strongly correlate with esophageal eosinophilia as well as previously described EoE transcriptome
  • Plasma miRNAs that are most differentiated in EoE include miR-146a, miR-146b, and miR-223.

Related posts:

Guidelines for Eosinophilic Esophagitis

Eosinophilic Esophagitis -Six Food Group Diet

The undiscovered country

Magnet ingestion –urgent removal needed

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This month’s Gastroenterology has an interesting picture of magnet(s) ingestion (Gastroenterology 2012; 142: 701, 1044).  This case report describes an ingestion by a 3-year-old boy who had swallowed 5 ball-shaped magnets.  The authors considered this an emergency even though it appeared that all 5 balls were in the stomach. As it turns out, a gastric mucosa fold was trapped in between the balls.  By taking the child for emergency removal, the authors averted a gastric perforation.

When multiple magnets are ingested, they may attract each other and cause pressure and subsequent damage. Magnet ingestion has become an important ingestion with case reports that have even included a death secondary to sepsis as well as perforations, fistulas, and volvulus.  Due to the potential for severe harm, they should be retrieved when possible ASAP.

Additional references:

Treatment for rumination and belching

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Treatment options for rumination and for belching are limited.  Baclofen improves symptoms and decreases events in both of these disorders (Clin Gastroenterol Hepatol 2012; 10: 379-84).

Rumination is characterized by effortless regurgitation of recently ingested food into the mouth (or beyond). It is easily mistaken for vomiting disorders and motility disturbances.  With rumination, patients have retrograde flow of gastric contents into the esophagus through voluntary, though unintentional, abdominal muscle contractions with increased intragastric pressure increases.

Supragastric belching occurs when air is sucked into the esophagus by decreasing the intrathoracic pressure or by contracting pharyngeal muscles.

Baclofen is an agonist of the γ-aminobutyric acid B (GABA) receptor which results in increased lower esophageal sphincter (LES) pressures and reduced swallowing rates. Baclofen has been shown to improve reflux, mainly by reducing transient LES relaxations (TLESRs) but also by increasing basal LES pressures.

In the majority of patients, the mainstay of treatment has been behavioral which use diaphragmatic breathing to compete/extinguish these behaviors.  There are a shortage of therapists familiar with this approach.  As such, alternative treatments are needed.  In this study, high-resolution manometry-impendance recordings were taken from 16 patients (10 women; mean age 43 years; range 18-89 years); eight of the patients had rumination.  Only 12 patients were included in the final analysis; four patients refused repeat manometry.  Manometry was performed before and after treatment along with recording symptoms.  Both symptoms and manometry recordings improved with Baclofen therapy.  This was a one-week open-label study.  Baclofen was dosed at 10 mg TID.  At baseline the total number of “flow events” was 473; after treatment, this was reduced to 282 events.  In total, rumination events decreased by 68% during treatment.   This improvement correlated with increased LES pressures.

Four of the 12 patients reported mild side effects mainly sleepiness and difficulty concentrating.

Additional references:

  • -Clin Gastroenterol & Hep 2007; 5:772. Review. Supragastric belching usually due to aerophagia and is very frequen (up to 20/hr)t. GERD related belching is less infrequent, has sour taste, usually less loud & after meals. Gum chewing, excessive beverage drinks, rapid eating or drinking,  smoking or using straw for drinking may increase air in the stomach and lead to burping which can be behavioural problem as well.
  • -“Behavioral Treatment of Chronic Belching Due to Aerophagia in a  Normal Adult” Behav Modif 2006; 30; 341
  • -JPGN 2011; 52: 414. Mgt of severe rumination @ Columbus Ohio. n=5. Definitive dx established with AD manometry with typical r-wave pattern (when regurgitates after a meal)
  • -JPGN 2010; 50: 103. Rumination occurring in NL intelligent adolescents. May start with regurgitation and progress to inability to swallow saliva.
  • -Clin Gastro & Hep 2006; 4: 1314. Review of management of rumination/case presentation
  • -Chitkara et al: Teaching diaphragmatic breathing for rumination syndrome. Am J Gastroenterol. 2006 Nov;101(11):2449-52. Review. Can use behavioral interventions such as deep breathing exercises/ diaphragmatic breathing to break the spasms..
  • -Gastroenterology 2006; 130: 1527-28. Review and criteria of rumination.
  • -Pediatrics 2003; 111: 158-62. Review of rumination dx, Rx, & prognosis.
  • -Clin Persp in Gastro 2000; 3 (5): 277.

Additional Baclofen references:

  • -J Pediatr 2006; 149: 436, 468. Baclofen reduces GER. 0.5mg/kg/day
  • -JPGN 2004; 38: 317. Effectiveness of baclofen in neurologically-impaired children w GER. (0.7/kg/day), n=8.
  • -Gastroenterology 2000; 118: 7-13. Use of baclofen to reduce TLESR.
  • -Aliment Pharm Ther 2003; 17: 243-51. Baclofen reduced GER (acid & nonacid). side effects -N, V, dizzy. dose: in adults, start at 5mg tid, increase c 5mg increments every 4th day to 10-20mg tid.

Outcomes of Biliary Atresia

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A retrospective study from the Netherlands showed that timely surgery and postoperative antibiotics were associated with better outcomes in Biliary Atresia (BA) (J Pediatr 2012; 160: 638-44).  While these results are not surprising, due to the length of the study period (1987-2008) and the number of patients (n=214), the study offers insight into a number of unresolved issues with regard to BA.

The type of BA in this series:

  • type I      14  (6.5%)
  • type II      27 (12.6%)
  • type III   172 (80.4%)
  • undetermined  1 (0.9%)

Other notable findings:

  • 10% of their patients had splenic malformations; no significant change in outcome was noted in this subgroup.
  • 18% received high-dose corticosteroids –no benefit was identified in this subgroup.  The authors state that previous studies are inconclusive; a large US trial of prednisolone (4 mg/kg/day initially) is pending.
  • 31% received ursodeoxycholic acid –no benefit was identified in this subgroup.
  • Overall survival improved a little during the study period, mostly due to increased availability of liver transplantation. 4-year transplant-free survival was 46% and 4-year overall survival was 73%.   Table II (pg 641) in their study lists six other international studies.  Recent studies in some countries have reported 4-year survivals of 82-91%.
  • Antibiotic usage (most commonly co-trimoxazole) was associated with improved outcomes, presumably due to less frequent bouts of cholangitis.  Yet, in this study the reported incidence of cholangitis was not lower.  The authors do not have an explanation for this finding.

Age at time of Kasai:

  • ≤45 days 19%
  • 46-60 days 37%
  • 61-89 days 36%
  • ≥90 days 8%
  • Median was 59 days.  Authors note that Netherland guidelines call for all infants with jaundice at 3 weeks to have a fractionated bilirubin.

Related blog entries:

Minimizing malnutrition in Biliary Atresia

The heart connection

MicroRNAs and biliary atresia

Additional references:

  • -JPGN 2010; 51: 631.  n=91.  Operation w/in 100 days.  Data suggesting that 60 day cutoff is not valid. (Hong Kong)
  • -J Pediatr Surg 2003; 38: 997-1000. n=735.  90 day cutoff was key with 5-yr & 10-yr survival. (Japan)
  • -JPGN 2010; 51:61.  Canadian experience. n=230.  Center size did not affect outcome.  Overall 39% at 4yrs had survival with native liver.
  • -Liver transplantation 2009; 15: 829, 876.  With combo of Kasai & Tx, >95% exteneded survival (previously 100% fatal).  >80% will need a liver Tx at some point –~50% before age 2.  Increased fibrosis & genes for fibrosis may increase risk for poor outcome.
  • -JPGN 2009; 48: 72.  Review of 13 year experience. n=91.
  • -Pediatrics 2008; 121: e1438.  Single center (Australia?) noted longer delay in dx of BA over 15-year period from 48.5 days (1990-94) to 59.5 (95-99) to 69 days (2000-2004).
  • -JPGN 2008; 46: 238, 299.  More data on age of dx of BA and outcomes from Sweden.
  • -J Pediatr 2006; 149: 393.  Long term outcome of BA -28yrs in England.  7/56 survived long term with native liver; 5-yr native liver survival was 46%, 10-yr was 32%.
  • -J Pediatr 2006; 148: 467, 432..  Outcome of BA in US.  Avg age of referral was 53 days and HPE avg at 61 days.  one-third will survive to age 10 with native liver; overall 90% survival with kasai/hpe & Tx; 50-60% clear jaundice p Kasai.  yellow alert campaign: www.childliverdisease.org/jaundice
  • -Clin Gastro & Hep 2006; 1411.  BA with choledochal cyst. Nice pics of types of BA. Japanese pathologic classification:  Type 1 with atresia after gallbladder (CBD), type II atresia of common hepatic duct/CBD/GB  c normal intrahepatic ducts, Type III atresia of entire ductal system.
  • -Pediartics 2006; 117: 1147.  Usefulness of stool color cards for screening program.
  • -J Pediatr 2005; 147: 142 & 180-5.  23% c BA survive c native liver for more than 20 yrs; 88% survival for 3 yrs p-OLT; risk factors for poor outcome discussed including poor nutrition & age <5 months.
  • -J Pediatr 2004; 144: 123-5.  severity of fibrosis at time of Kasai inversely correlated with survival
  • -JPGN 2003; 37: 430-33.  Residual fibrosis/cirrhosis noted in 54%/40% respectively of pts with normal labs, median age 13 yrs.
  • -JPGN 2003; 37: 4-21. Review of BA

Cardiovascular disease for the entire family

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This month’s Journal of Pediatrics features an article for the entire family (J Pediatr 2012; 160: 590-7 [editorial pg 539]).  The authors demonstrate that children screened for cholesterol can serve as an index case for the entire family.  During a 26-year prospective followup of 852 pediatric patients (5-19 years old at enrollment) from Cincinnati, the authors assessed relationships of childhood risk factors with parental cardiovascular disease (CVD), type 2 diabetes (T2DM), and high blood pressure (HBP).

  • Pediatric HBP and low HDL cholesterol were predictive of parental CVD ≤age 50
  • Pediatric HBP and high triglycerides were predictive of parental CVD ≤age 60
  • Pediatric high triglycerides and high LDL cholesterol were predictive of parental CVD ≤age 66

The related editorial reviews large studies regarding lipid assessments, including the Bogalusa study with more than 3000 children and the Muscatine study with more than 14,000 children.  In addition, the editorial reviews the recommendations from an expert pediatric panel which suggested screening all children for dyslipidemia between 9 and 11 years. Interestingly, the editorial reviews the fact that screening for cholesterol has not been shown to harm children.  “The evidence is not sufficient to demonstrate any adverse affects.”

Although no harm has been proven, the expert recommendations do not have prospective data demonstrating benefit either.  While it is known that atherosclerotic lesions, including fatty streaks and calcifications, can develop in childhood, it is not known that current treatment strategies will improve long-term outcomes.  This study, however, provides an additional rationale for screening; namely, by identifying children with dyslipidemia, primary care providers can identify parents with cardiovascular disease who are more likely to benefit from urgent intervention.

Additional references:

  • http://hin.nhlbi.nih.gov/atpiii/calculator.asp?usertype=prof (cholesterol risk calculator)
  • Pediatrics 2011; 128 (suppl 5): S213-56.  Expert panel guidelines for cardiovascular health and risk reduction in children and adolescents.
  • -NEJM 2011; 365: 2078.  Use of statins to lower LDL to 60-70 range halted progression of coronary artery disease.
  • -Pediatrics 2007; 120: e189, e215.  US Preventive Services Task Force:  “the evidence is insufficient to recommend for or against routine screening for lipid disorders” up to age 20.  Consider pediatric drug Rx:
    1. After dietary failure
    2. LDL >190
    3. LDL >160 & FHx of CVD before age 55
    4. triglycerides >250-500 persistently
  • Pediatric Nutrition Handbook AAP Lipid types:type I -increased trig  (rare)
    type IIa -increased chol & LDL
    (most common)
       Homozygous: chol >500
         xanthomas before 10 yrs, vascular dz before age 20
       Heterozygotes with lower chol
    type IIb -elevated trig & chol/LDL
    (3rd most common)
    type III -abnormal LDL density (rare)
    type IV -elevated trig (2nd most common)
         may be increased with diabetes, obesity, inadequate fasting; may need to study parents to establish dx
    type V -increased trig/VLDL (rare)
         exclude nephrotic synd, hypothyroid, diabetes

Save a life with free allergy education

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Food allergy affects 4-8% of children and allergic reactions can be fatal.  In fact, the main cause of poor outcome with accidental food allergy exposure is delay in the use of epinephrine.  To improve parental knowledge and overall management of food allergies, a group of allergists, nurses and dieticians has developed and validated educational materials (J Pediatr 2012; 160: 651-6).  In addition, they have made these materials available at no cost online:

To validate their materials, the authors enrolled 60 parents of newly referred children with a prior food allergy.  The measured outcome was demonstration of an autoinjector for epinephrine.  The correct number of steps in the use of the autoinjector increased from a 3.4 to 5.95 score (max score 6).  In addition, at 1 year, the score remained high, 5.47.  Knowledge tests improved as well: from 9.2 to 12.4 (out of 15); at one year, the score was 12.7.  On a practical basis, the frequency of allergic reactions was reduced as well.  The annualized allergic reaction rate dropped from 1.77 (historical data) to 0.42 after the instruction.

The article also relates that some of the material relied on previous educational material, in particular the food allergy emergency plan available from the Food Allergy & Anaphylaxis Network (www.foodallergy.org).

Materials available include information on specific allergic disorders, avoiding allergens, management in and outside home, and living a safe/healthy life.  In addition, an educational video is available.

Additional references:

  • -Bock SA et al. J Allergy Clin Immunol 2007; 119: 1016-8. Poor outcome with accidental food allergy exposure is delay in the use of epinephrine.
  • -J Pediatr 2011; 158: 578.  Oral food challenges allowed 84% to return foods to diet.  n=125.
  • -Clin Gastro & Hep 2010; 8: 755.  Review of food allergy (vs intolerance) in adults.  Gives list of hypoallergenic diet , pg 758.
  • -Pediatrics 2009; 124: 1549-55.  3.9% of US kids w food allergy.  Nat’l surveys.
  • -NEJM 2008; 359: 1252 Review. Usual age of resolution: eggs  @ 7yr (75%), milk @ 5yr (76%); wheat/soy -rarely cause IgE-mediated allergies 80% resolve by 5yrs>  More  persistent allergens:  peanuts/tree nuts/sesame seeds = persistent in 80-90% at 5yrs, fish = persistent.
  • -Pediatrics 2003; 111: 1591-1680.  (supplement) Pediatric Good Allergy symposium
  • -Pediatrics 2003; 111:829-835. Infants c food-induced enterocolitis often have multiple food allergies (cereal, veggie, poultry, meat)  IgE based tests are negative (skin prick & IgE Abs
  • -Gastroenterology 2001; 120: 1023-25; 1026-40.  AGA position paper; technical review.
  • -J Allergy Clin Immmunol 1999; 103: 717-728 &981-9.  Pathogenesis &  Dx/ mgt.

Guidelines for Eosinophilic Esophagitis

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For a little while, I’ve meant to complete a post on the EoE guidelines published last fall (J Allergy Clin Immunol 2011; 128: 3-20).  This article, based on the input of 33 physicians with EoE expertise, provides a lot of depth to this unfolding area in pediatric gastroenterology.

Diagnosis of EoE. The authors caution that this diagnosis is not a histologic diagnosis as a number of entities can cause esophageal eosinophilia; at the same time, a minimum number of eosinophils, 15/hpf, is a necessary diagnostic threshold.  A small number of patients may have EoE with fewer than 15/hpf, including PPI-responsive EoE, inadequate biopsy sampling, seasonal variation, or partial treatment (eg. patient on corticosteroids).

How many biopsies?  In one cited study in the article, 2, 3, and 6 biopsies had sensitivity of 84%, 97%, and 100% respectively.  Endoscopic biopsies remain the only reliable diagnostic test.

Why are there a subset of PPI-responsive EoE patients?  Potential explanations include improvement in immune-activation after healing of esophageal mucosa, inherent anti-inflammatory property of PPIs, or due to pitfalls in current diagnostic testing.  Due to recognition of this disorder, pH testing may be needed in many patients with suspected EoE.  Even still, the authors note that “PPI responsiveness or diagnostic testing (pH monitoring) might not adequately distinguish GERD and EoE.”

How useful are genotypic features?  Clinical  use of genotypes is not feasible at this time.  However, it is anticipated that esophageal gene expression will emerge as one way to differentiate EoE from other conditions and to determine optimal treatments.

What type of allergy evaluation? The majority of EoE patients have concurrent atopic diseases, including rhinitis, asthma, and eczema.  Thorough evaluation by an allergist (or immunologist) is recommended.  Specific recommendations: skin prick testing (SPT), serum IgE for immediate-type food allergy.  Atopy patch testing (APT) has high negative predictive values, >90%, except for milk which is ~50%.  APT needs to “be standardized and validated.”

Biomarkers? “Insufficient evidence to support any peripheral marker” including cytokines, and IgE (total).

Treatment –PPI: PPIs are useful to distinguish GERD as well as PPI-responsive EoE from EoE requiring other treatments.  They also help with symptomatic treatment in some patients who have secondary GERD.  Recommended dose in children 1 mg/kg/dose BID.

Treatment –Dietary: Three dietary regimens have potential effectiveness: 1) selective food diet based on allergy testing, 2) dietary restriction of the most likely food antigens (eg. six food group diet elimination) and 3) strict amino acid based diet.  Tolerance of foods that have been shown previously to provoke EoE is unlikely to develop in the majority of EoE patients.

Treatment –Corticosteroids: Corticosteroids are effective but when discontinued EoE almost always recurs.  Systemic corticosteroids can be particularly useful when severe dysphagia is present.  With severe endoscopic findings, a course of corticosteroids may help reduce the need for dilatation or lessen the risk.  Long-term use of systemic steroids is not recommended.  Topical steroids should be considered in all patients with EoE.  Recommended doses are given.

  • For fluticasone:  88-440 μg 2-4 times per day (max 880 μg BID)
  • For budesonide: 1mg daily (<10 y) and 2 mg daily (≥10 y)
Treatment –Dilation:  Dilation can provide relief of dysphagia.  In most cases, medical or dietary therapy should be attempted prior to use of dilation.  Goal of 15-18 mm.  Practical advice (not validated in studies): Limit dilation progression per session to 3 mm or less after resistance has been encountered.
Treatment –Alternatives:  Cromolyn, leukotriene receptor antagonists, or immunosuppressive agents (eg azathioprine, 6-mercaptopurine) are “not recommended.”
Complications: Perforations (spontaneous & procedure-related), food impactions, strictures, and narrow caliber esophagus.  There has not been evidence of an increased esophageal cancer risk in EoE patients to date.
Unresolved issues: Despite the extensive consensus on many of these issues, the conclusions inform the reader of how far we need to go.  Some of the unresolved questions include such basic problems:
  • “Importance of treating asymptomatic patients”
  • “Natural history of EoE and rates and predictive indexes of complications”
  • “Accuracy of skin prick and patch testing”
  • “Optimal end points of treatment”

Previous related blog posts:

The undiscovered country

Eosinophilic Esophagitis -Six Food Group Diet

Practical information on EoE for families:

http://www.ccdhc.org/diseases/EoE.html

Biomarkers identify patients who benefit and how

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Fecal calprotectin and serum CRP levels are helping to identify which patients benefit most from biologic therapies, how frequently to dose individuals and how well inflammation correlates with changes in CDAI.  Several abstracts from ACG highlight these issues:

Abstract #1175: Fecal calprotectin concentration and clinical remission in patients with active Crohn’s disease treated with certolizumab pegol: results from PRECiSE 1 (Sandborn W et al).

Abstract #1164: Baseline C-reactive protein is associated with disease progression in  patients with Crohn’s disease (Colmbel J-F et al).

Abstract #1165: Association of baseline C-reactive protein with maintenance of remission in patients with moderate to severe Crohn’s disease treated with adalimumab (Sandborn W et al)

Abstract 1175 uses a post hoc analysis of patients with active Crohn’s disease (CD) who were treated with certolizumab or placebo for 26 weeks.  Baseline calprotectin concentrations were higher in patients who achieved remission.  Another interesting finding of this study was that placebo patients did not have improvement in calprotectin levels.  So, even though some patients  had improvement in CDAI scores, indicating subjective improvement, inflammatory activity did not decline.  This is another indicator of how flawed a CDAI is for indicating the effectiveness of an IBD therapy.

Abstract 1164 looked at 238 patients with moderate to severe CD who were randomized to placebo arm in the CHARM study.  These patients were given open-label adalimumab for induction (80 mg week 0, 40 mg week 2) followed by blinded weekly placebo treatment from weeks 4-56 with a switch to open-label adalimumab after week 12 for a disease flare.  Higher baseline CRP levels in patients with moderate or severe CD were associated with higher disease scores after four weeks and after one year.  This suggests that a patient with higher CRP is more likely to have disease progression without adequate treatment.

Abstract 1165 examined the relationship between CRP and remission in CHARM patients. In the high baseline CRP group, 39 patients received adalimumab every other week, 28 weekly, and 34 received placebo.  In the low baseline CRP group, there were 42 every other week patients, 33 weekly, and 39 placebo patients.  In the high baseline CRP group, remission rates were 50% higher in the weekly treatment group compared to the every other week group.  Patients with low baseline CRP had similar results when treated weekly versus every other week.  Thus, patients with high baseline CRP are more likely to benefit from dose escalation and low CRP patients are more likely to have coexistent issues contributing to their symptoms (eg. IBS).

One other caveat: CRP production is geneticallly-determined and some patients do not make CRP in spite of active inflammation.

Related blog entries:

Food as medicine

Speed matters

Additional calprotectin references:

  • -IBD 2010; 16: 482. Calprotectin correlated with inflammation of ileum after pouch creation in children.
  • -IBD 2009; 12: 1851. Calprotectin was the only marker to correlate with endoscopic activity; n=134.
  • -JPGN 2009; 48: 48. Good sensitivity/specificity of calprotectin & lactoferrin. Up to 96% sensitivity & specificity.
  • -Clin Gastro & Hep 2008; 6: 1218. Lack of correlation between clinical symptoms and fecal biomarkers. However, biomarkers do correlate with mucosal/endoscopic disease. n=164.
  • -IBD 2008; 14: 1392. Monitoring IBD activity level c calprotectin & lactoferrin; n=15.
  • -IBD 2008; 14: 1229. Clinical utility in assessing histological relapse in kids. n=73 over 8yrs…may allow avoidance of invasive tests; cut off of 275mcg/gm had 97% sensitivity/neg pred value 85% pos pred value/specificity at predicting relapse.
  • -IBD 2008; 14: 669. Fecal calprotectin good at predicting relapse in pediatric IBD w cutoff of 400.

C-reactive protein references:

  • -J Pediatr 2011; 159: 340. CRP helps identify IBD.
  • -Clin Gastro & Hepatology 2011; 9: 421. CRP predicts response to IFX. n=718. those with high CRP had 91% response vs 83% in pts with NL CRP.
  • -Gastro 2004; 126: 1574-81. Crohn’s review. High CRP suggests likely response to anti-TNFα treatment.
  • -JPGN 2004; 38: 509-12. CRP more reliable than ESR for IBD.
  • -NEJM 1999; 340: 448. Review on acute phase reactants. CRP better than ESR as ESR is an indirect measure (resistance of plasma, due to fibrinogen, to the falling of RBCs) & broader range for CRP.