Author Archives: gutsandgrowth

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About gutsandgrowth

I am a pediatric gastroenterologist at GI Care for Kids (previously called CCDHC) in Atlanta, Georgia. The goal of my blog is to share some of my reading in my field more broadly. In addition, I wanted to provide my voice to a wide range of topics that often have inaccurate or incomplete information. Before starting this blog in 2011, I would tear out articles from journals and/or keep notes in a palm pilot. This blog helps provide an updated source of information that is easy to access and search, along with links to useful multimedia sources. I was born and raised in Chattanooga. After graduating from the University of Virginia, I attended Baylor College of Medicine. I completed residency and fellowship training at the University of Cincinnati at the Children’s Hospital Medical Center. I received funding from the National Institutes of Health for molecular biology research of the gastrointestinal tract. During my fellowship, I had the opportunity to work with some of the most amazing pediatric gastroenterologists and mentors. Some of these individuals included Mitchell Cohen, William Balistreri, James Heubi, Jorge Bezerra, Colin Rudolph, John Bucuvalas, and Michael Farrell. I am grateful for their teaching and their friendship. During my training with their help, I received a nationwide award for the best research by a GI fellow. I have authored numerous publications/presentations including original research, case reports, review articles, and textbook chapters on various pediatric gastrointestinal problems. In addition, I have been recognized by Atlanta Magazine as a "Top Doctor" in my field multiple times. Currently, I am the vice chair of the section of nutrition for the Georgia Chapter of the American Academy of Pediatrics. In addition, I am an adjunct Associate Clinical Professor of Pediatrics at Emory University School of Medicine. Other society memberships have included the North American Society for Pediatric Gastroenterology Hepatology and Nutrition (NASPGHAN), American Academy of Pediatrics, the Food Allergy Network, the American Gastroenterology Association, the American Association for the Study of Liver Diseases, and the Crohn’s and Colitis Foundation. As part of a national pediatric GI organization called NASPGHAN (and its affiliated website GIKids), I have helped develop educational materials on a wide-range of gastrointestinal and liver diseases which are used across the country. Also, I have been an invited speaker for national campaigns to improve the evaluation and treatment of gastroesophageal reflux disease, celiac disease, eosinophilic esophagitis, hepatitis C, and inflammatory bowel disease (IBD). Some information on these topics has been posted at my work website, www.gicareforkids.com, which has links to multiple other useful resources. I am fortunate to work at GI Care For Kids. Our group has 17 terrific physicians with a wide range of subspecialization, including liver diseases, feeding disorders, eosinophilic diseases, inflammatory bowel disease, cystic fibrosis, DiGeorge/22q, celiac disease, and motility disorders. Many of our physicians are recognized nationally for their achievements. Our group of physicians have worked closely together for many years. None of the physicians in our group have ever left to join other groups. I have also worked with the same nurse (Bernadette) since I moved to Atlanta in 1997. For many families, more practical matters about our office include the following: – 14 office/satellite locations – physicians who speak Spanish – cutting edge research – on-site nutritionists – on-site psychology support for abdominal pain and feeding disorders – participation in ImproveCareNow to better the outcomes for children with inflammatory bowel disease – office endoscopy suite (lower costs and easier scheduling) – office infusion center (lower costs and easier for families) – easy access to nursing advice (each physician has at least one nurse) I am married and have two sons (both adults). I like to read, walk/hike, bike, swim, and play tennis with my free time. I do not have any financial relationships with pharmaceutical companies or other financial relationships to disclose. I have helped enroll patients in industry-sponsored research studies.

Understanding IL28B

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Interleukin-28B (IL28B) has been a phenomenal discovery in the field of hepatitis C (HCV); yet, with the emergence of direct-acting antiviral (DAA) agents, its importance has been overshadowed.  While the long-term significance of IL28B is unclear, for now, it has significant clinical utility.  Three reviews/commentaries help elucidate its role:

▪                Hepatology 2012; 56: 361-66. IL 28B Genetics and Biology

▪                Hepatology 2012; 56: 367-372 Clinical Utility of IL28B

▪                Hepatology 2012; 56:  373-380 Relevance of IL28B in age of DAAs

Key points from these references:

African-Americans are less likely to respond to treatment with pegylated interferon (PEGIFN) (and ribavirin [RBV]) in large part due to a low frequency of favorable alleles (C/C genotype) to IL28B.

Predictors of response to treatment with PEGIFN/RBV:

▪                CC IL28B genotype: OR 5.9 (compared to non-CC genotype)

▪                HCV RNA level ≤600,000 IU/mL: OR 3.1 (compared to >600,000 IU/mL)

▪                Degree of fibrosis, metavir F0-2: OR 2.7 (compared with F3-F4)

▪                Rapid virological response: OR 9.1 (compared with non-RVR non CC genotype)

Overall CC genotype is associated with double the sustained virological response (SVR).

Vitamin D also plays an important role in innate immunity and deficiency is associated with lower SVR.

Algorithm for use of IL28B (applicable to patients ≥18 years):

▪                Consider obtaining IL28B in all genotype 1 patients:  

▪                If CC genotype and does not have risk factors for poor response (including cirrhosis, high viral load), then likely to treat with PEGIFN/RBV and monitor for RVR.  In patients without RVR, addition of DAA would be reasonable.

▪                If risk factors for poor response or if non-CC genotype (C/T or T/T), then consider use of DAA at onset of therapy

DAAs are expensive.  Boceprevir (BOC) costs $26,000 for 24 weeks & $48,000 for 44 weeks.  Telaprevir (TVR) costs $49,000 for 12 weeks.  These costs are in addition to costs for PEGIFN/RBV which is approximately $30,000.  The cost of testing IL28B status is approximately $300.

In patients with CC IL28B genotype, the main advantage of DAAs may be to shorten treatment course by increasing the likelihood of RVR; though with TVR, the SVR was improved even among CC genotype patients in the “ADVANCE” trial (90% compared with 64%).  In non-CC IL28B genotype, TVR or BOC is associated with > 2-fold increase in SVR.  The specific response rates for both TVR and BOC are available in these references.

Related blog entries

Pediatric HCV Guidelines

Increased ferritin predicts poor response in Hepatitis C

Unknown unknowns for Hepatitis C

HCV now more deadly than HIV

The cost of progress in treating Hepatitis C

Adalimumab for children with Crohn’s disease

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While adalimumab has been used in children with refractory Crohn’s disease, there has not been a lot of available data.  However, this situation has improved with the publication of the “IMAgINE 1” study (Hyams JS et al, Gastroenterology 2012; 143: 365-74).

This study enrolled 192 pediatric (6-17 yr-old) patients with moderate to severe Crohn’s disease; patients had PCDAI >30 and had failed conventional therapy with the exception of infliximab.  Approximately 45% in both groups had received prior treatment with infliximab.  The study started as an open-label induction followed by double-blind randomization into either a high-dose or low-dose maintenance phase.

Dosing:  For open label, patients >40 kg received 160 mg at week 0 and 80 mg at week 2.; patients <40 kg, received 80 mg at week 0 and 40 mg at week 2.

For maintenance, high dose was considered 40 mg every other week (eow) if >40 kg, and 20 mg eow if <40 kg.  Low dose was 20 mg and 10 mg respectively based on weight.

Results: 152 of 188 patients completed 26 week study period; 4 patients did not complete induction period.  At week 26, 63 patients (33.5%) were in clinical remission.  The high-dose remission response was 38.7% which was not statistically different from the 28.4% response in the low-dose group.

At week 52, there was a statistically improved response rate in the high-dose group 41.9% compared with low-dose group 28.4%; at the week 52 point, the remission rates were 33.3% compared with 23.2% respectively (p=0.1).  Among patients who were at least 13, it is noted that the overall CDAI clinical remission rate was 51% (week 26) and 36% (week 52) which are comparable to adult data from CHARM study.

Based on previous infliximab: Patients who had prior infliximab did not respond as favorably as infliximab-naive patients.  In the high dose group, the clinical remission at week 26 was 56.9% for infliximab-naive group compared to 16.7% for infliximab-experienced.  Similarly, the infliximab-naive response was higher, 68.6% compared with 47.6% for the infliximab-experienced.

Safety: “No new safety signals were detected.” Yet, 101 of 192 patients had adverse events during open label period, including 2 serious infections (which resolved & patients completed study).  Eight serious infections were noted during double-blind period.  Other safety problems included hepatic-related events in 9 of 188 patients, injection site reactions in 19 patients, hematologic adverse events in 8 patients, and 8 allergic reactions.  There were no reports of malignancy, congestive heart failure, lupus-like syndrome or demyelinating disease.

In both the high-dose and low-dose group, switching to weekly therapy instead of eow was allowed and commonly occurred: 48/95 in low-dose & 35/93 in high-dose.

Reasons for discontinuation: In both groups, drug discontinuation was frequent.  In the low-dose group, 37 patients stopped therapy.  In 18, this was due to lack of efficacy.  The other reasons included adverse effects in 10, protocol violation in 4, withdrew consent in 4, and lost to followup in 1.  In the high-dose group, 27  stopped therapy.  In 11, this was due to lack of efficacy; 12 had adverse effects, 2 withdrew consent, and 1 had protocol violation.

Another recent article (Inflamm Bowel Dis 2012; 18: 685-90) indicates that the annual risk of loss of response to adalimumab was 18% per year of followup.  This study involved 380 CD patients with an average age of 38 years.  This study also showed that there was a significant difference between patients naive to anti-TNF therapy and those who had prior anti-TNF therapy:  8% loss of response per year of followup compared with 22% respectively.

Related blog entries:

TNF-α antagonists and infections

CHOOSE TNF TRIAL

Disease modifying treatment in IBD

Only one chance to make first impression

TNF antagonists and UC

Adalimumab references:

  • -Gut 2011:  Gut doi:10.1136/gut.2010.221127. Use in induction of remission in UC. Reinisch W, et al. Adalimumab for induction of clinical remission in … – Gut – BMJ
  • -Aliment Pharmacol Ther 2010; 32: 1228-39. CHOICE trial. adalimumab effective in pts failing prior IFX.
  • -Gastroenterol 2009; 137: 1628. n=168.  71% & 67% of pts responded by weeks 4 & 12.  61% demonstrated sustained benefit. (in IFX failure pts). Of 156 pts, 65% needed to step up to 40mg weekly and 60 eventually stopped adalimumab due to loss of response.  Lower trough levels associated with loss of effectiveness & often with antibodies to adalimumab (present in 9.2% of pts).
  • -IBD 2011; 17: 2512.  n=50.  62% of pts develop skin reactions: eczema, acne-like dermatitis, psoriasis-like (6 of 50).  Adalimumab d/c’d in 22%.  Message -see dermatologist
  • -Lofberg et al. Am J Gastro 2008; 103: S418 (abstract 1069) Care study. -n=945. Humira at week 20 -remissions in 52% of pts naive to biologics, in 46% who prev responded to IFX & became intolerant, in 40% who prev responded to IFX and lost response, and 36% of pts with primary non-response to IFX.
  • -IBD 2008; 14: S1 Abrstarct 0002. Humira in TNF-naive patients with Crohn’s disease. Decreases hospitalizations. (12 month: 12.7% vs 20.3% in placebo group) Adult dosing: Induction 160mg, then 80mg in 2 weeks, then 40mg every 2 weeks.
  • -IBD 2008; 14: 1683. Response to adalimumab in 10 children.
  • -Gastro 2008; 135: 1493. n=778. mod-to severe Crohn had less hospitalizations (decreased ~60%) and surgery if Rx’d w Humira. 40mg eo week or qweek post 80/40 induction
  • -NEJM 2008; 359: 810. Use in pediatric JRA -helpful.
  • -JPGN 2008; 47: 19. n=15 pediatric patients. Complete or partial response in 64%.
  • -Gastro 2007; 132: 52. CHARM Trial. n=778. 40mg weekly c 47% response at week 26 (17% placebo) & 41% @ week 52 (12% placebo); works nearly as well in pts c prev inliximab as naive pts. Rapid onset ~c/in 2 weeks
  • -Clin Gastro & Hep 2006; 4: 1199-1213. Excellent review. Suggested dosing: 20mg every other week if 20-25kg, 25mg every other week if 25-30kg, 30mg every other week if 30-40kg, 35mg every other week if 40-55kg,  40mg every other week if >55kg, and increase to weekly dosing if needed
  • -JPGN 2008; 46: 1208, 226. pediatric case report and review of CHARM
  • -Gastro 2006; 130: 323-333. CLASSIC-I Trial, n=299. 36% 4-week response to 160mg/80mg week 0/subsequent week 2 (vs. 12% of placebo) All pts naive to anti-TNF Rx.

Adalimumab Injection Pain

  • –Suggestions from GI bulletin board. 1)you let the Humira Pen sit out for about 30 minutes prior to administering the medication, so that it appears clear and not foggy, that it greatly reduces pain at the site. 2) the pain disappeared after adding bicarbonate to the Humira. By trial and error, our nurse found that 0.15cc of bicarbonate is the minimum amount that yields a good effect.
  • -Lidocaine with adalimumab. Abstract reference: AF Ayala, Rosanne S.Groh, Brandt P.Robbins, Lisa M.Scalzi, Lizabeth Bingham, C. April TI The addition of injectable lidocaine to adalimumab results in decreased injection site pain and increased acceptance of therapy. 72nd Annual Scientific Meeting of the American-College-of-Rheumatology/43rd Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals. CY OCT 24-29, 2008 CL San Francisco, CA. They used 0.2 ml 1% lidocaine into prefilled adalimumab syringe. We’ve tried this with a few patients and it seems to work well.
  • -Pt developed a “shot blocker” that is a bristle brush with a central hole for the syringe. The brush diffuses the pain from the Humira injection. Click the link below for a youtube video he created.
  • -http://www.youtube.com/watch?v=nfL95YRlTjY

Salt for POTS –who benefits?

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Individuals with postural orthostatic tachycardia syndrome (POTS) who have low baseline urinary sodium excretion (<124 mmol/24 hours) were more likely to benefit from sodium supplementation (J Pediatr 2012; 161: 281-4). In this group, “as much as 90% of patients” will improve with salt supplements.

This study from China examined the effects of sodium supplementation in 30 children (20 females, 10 males) as well as in 10 control patients to identify factors which related to therapeutic response.  Criteria for POTS included orthostatic intolerance (without orthostatic hypotension –blood pressure drop >20/10 mm Hg) accompanied by a heart rate increase of >30/min within the first 10 minutes of standing.

Despite normal serum sodium, POTS cohort had baseline 24-hr sodium excretion of 117 ± 59 compared with control of 194 ± 91.  POTS sodium-responders were similar in all aspects at baseline except for lower sodium excretion: 85 ± 35 compared to 150 ± 51 for POTS sodium-nonresponders.

The discussion reviews the theoretical reasons for POTS response to sodium (e.g.. ‘relative hypovolemia’) and points out that there are several subtypes, including ‘hypovolemic,’ hyper-adrenergic,’ and ‘autoimmune.’ Salt supplementation which has been shown to be effective only in the pediatric population targets the hypovolemic subset.

Limitations:

  • Small sample size
  • Lower sodium excreters had more symptoms at baseline & therefore may have led to bias as well

Additional references:

  • -J Pediatr 2011; 158: 20 (pg 4 editorial). n=53. GI pain in 75%, nausea/vomiting in large fraction, sleeping problems in 98%, headache, syncope, urinary symptoms. May have poor stomach emptying due to autonomic dysfunction
  • -J Pediatr Gastroenterol Nutr. 2010 Sep;51(3):314-8. Gisela Chelimsky  “Gastric Electrical Activity Becomes Abnormal in the Upright Position in Patients With Postural Tachycardia Syndrome”
  • -J Pediatr 2011; 158: 499. Orthostatic hypotension can be treated physically: gripping hands for 15 secs before rising, lower body muscle contraction (eg pumping calf muscles/tensing legs), squatting…

Why Pertusis is resurgent –it’s not what you think

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What are the reasons why pertusis, a vaccine-preventable disease, is epidemic?

According to an editorial by James Cherry (NEJM 2012; 367: 785-87), there are four main reasons.

  • 1) Increased awareness
  • 2) Easier detection with PCR assays
  • 3) Increased use of less potent vaccines, mainly DTaP
  • 4) Possible genetic changes in B pertusis

Useful epidemiology information:

  • 13-20% of adolescents and adults with prolonged cough have B pertusis.
  • Lowest incidence was reported in 1973: 1 per 100,000.
  • In prevaccine era, B pertusis had pattern of epidemics every 2 to 5 years, with peak incidence of 157 per 100,000.
  • In 2010, incidence was 9 per 100,000
  • Neither infection or immunization provides lifelong immunity

His recommendations/conclusions:

  • We need to use the vaccines we have.  This is necessary to avoid the ‘frightening rates of complications and death’ associated with pertusis in infants.
  • Consider starting immunization at an earlier age –1st three doses could be completed by 3 months of age
  • Improved vaccines are needed

Related blog entries:

Protecting the most vulnerable

Hepatitis A vaccine immunity –will it last?

How to stop HBV vertical transmission

Epidemic of Prescription Drug Overdoses

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More information on the epidemic of drug overdoses: MMWR 2012: 61: 10-13.

In 2007, in U.S. one death due to unintentional drug overdose occurred every 19 minutes (27,000 cases), primarily due to opioid analgesics.  In addition, for every death, there were nine persons admitted for drug treatment, and 35 emergency room visits.

The escalating drug use can be quantified.  In 1997, drug distribution through pharmacies delivered the equivalent of 96 mg of morphine per person whereas in 2007 the amount was 700 mg per person; 700 mg is enough for every person in U.S. to receive a three-week course of Vicodin (hydrocodone/acetaminophen 5mg q4 hours).

Only 10% of these patients were seeking care from multiple doctors; yet this 10% accounted for 40% of the cases of overdosage.

Prevention strategies:

  • Prescription data to prevent doctor shopping & reduce inappropriate use of opioids/selling excessive opioid prescriptions
  • Enforcing laws against ‘pill mills’
  • Improve medical practice in prescribing opioids

Additional references/previous blog entries:

Epidemic: Responding to America’s Prescription Drug Abuse Crisis  Whitehouse plan

Pediatric pharmaceutical poisoning

Deadly consequences of pain management

Why “therapeutic dose” of codeine can kill

Vedolizumab -another new IBD treatment

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Occasionally a parent will express concern that their child may run out of effective treatments for inflammatory bowel.  At this time, there are a limited number of effective therapies. If a patient develops reactions or antibodies to medications and/or does not have a clinical response, then the options become quite limited.

Against this backdrop, it is encouraging that new medical treatments are being tested, including Vedolizumab (Inflamm Bowel Dis 2012; 18: 1470-79).

The cited study reports the experience of using Vedolizumab in a randomized controlled phase 2 dose-ranging study in 46 patients (9 placebo, 37 vedolizumab).

Vedolizumab is “a gut-selective monoclonal antibody that antagonizes α4β7 integrin on select subsets of leukocytes binding to MAdCAM-1 on gut vascular endothelium.”  Many have considered vedolizumab to be similar to natalizumab, except it is considered  gut-specific and therefore should not increase the risk of progressive multifocal leukoencephalopathy (PML).  By altering the immune surveillance/lymphocyte tracking of the GI tract and not the brain, theoretically there should not be an increased risk of PML.

Another previous limitation of vedolizumab in small studies was the development of human antihuman antibodies (HAHA) –no joke!  HAHA occurred in up to 44% of patients in previous studies and were associated with reduced efficacy.  As a consequence, a new formulation of vedolizumab has been developed with presumably reduced  immunogenicity.

In the cited study, patients between 18-70 were recruited to receive one to three doses of vedolizumab (2, 6, or 10 mg/kg) or placebo.

Results:

  • Over 50% of vedolizumab-treated patients maintained a clinical response between days 29-253 whereas placebo response ranged between 22-33%.
  • This study was not powered for efficacy; however, the treated patients did have reduced fecal calprotectin.  At baseline, the calprotectin in the treatment groups averaged 405 μg/g and by day 113 had reduced to 54 μg/g.  In contrast, placebo group started with calprotectin of 310 μg/g and dropped to 192 μg/g during same time period.
  • HAHA were detected in 4 (11%)

According to a presentation at DDW (GEMINI I trial), more than 2500 patients have been treated in trials with vedolizumab.  None has developed PML. Encouraging results for efficacy (dosing 300mg IV q4weeks) were also noted; 1 year clinical remission noted in 45% of treated patients compared with 14% of placebo group. Digestive Disease Week 2012 – Vedolizumab Scores on Safety …)

Results of vedolizumab for Crohn’s disease are expected soon as well.

Related blog entries:

Quantifying Risk of PML with Natalizumab

Tofacitinib –a JAK Inhibitor for UC

Effects of pegylated interferon on growth

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Besides examining the effectiveness of pegylated interferon for hepatitis C virus (HCV) in children, the PEDS-C (Pediatric Study of Hepatitis C) trial data has been studied to determine the effects of pegylated interferon (PEG) on growth and body composition (Hepatology 2012; 56: 523-31).

In this study of 114 children who were treated with PEG along with ribavirin (RBV), anthropometric measurements, dual-energy X-ray absorptiometry, dietary intakes, and activity assessments were performed.  Of the initial 114 children (5-18 years), 107 received treatment for more than 24 weeks: 14 for 24 weeks, 82 for 48 weeks, and 11 for 72 weeks.

In the group treated for 48 weeks, 29 (33%) had more than a 0.5 unit decrement in height-for-age score (HAZ).  Based on figure 2 in the study, most of the HAZ decrement at 48 weeks and resolved at 144 weeks (time after treatment initiation).  In contrast, weight-for-age and BMI scores returned to baseline after stopping HCV therapy.  The authors note that while most growth parameters generally were “reversible with cessation of therapy…HAZ scores had not returned to baseline after 2 years of observation in many.”

Another observation from the study was that weight and height decreased in tandem.  In contrast to sequential change, this type of change indicates that other mechanisms besides poor intake are likely affecting linear growth.  These HAZ effects were noted in adolescents; there was no difference in HAZ scores in preadolescent patients.

The potential effects on growth may influence the timing of therapy.  At the same time, as new HCV treatments are studied in pediatric patients, the effects of interferon may become a moot point.

Related blog entries

Pediatric HCV Guidelines

Understanding IL28B

Increased ferritin predicts poor response in Hepatitis C

Unknown unknowns for Hepatitis C

CHOOSE TNF TRIAL

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While most physicians consider drug efficacy as the most important factor in choosing therapy, this is not always the determinant factor in patient choice.

The “CHOOSE TNF TRIAL” (Inflamm Bowel Dis 2012; 18: 1523-30) was a prospective survey of 100 adult patients with Crohn’s disease who were naive to anti-TNF therapy (infliximab, adalimumab, certolizumab).

Most important to patients:

  • Ease of use 69%
  • Time for therapy 34%
  • Time between applications 31%
  • Evidence for efficacy 19%
  • Fear of syringes 10%

Patient choice: Adalimumab preferred in 36%, certolizumab in 28%, and infliximab in 25%

While patient concerns need to be considered, others have shown that physician opinion is an important factor for patient decisions (J Rhemumatol 2008; 35: 618-24).  The discussion notes that “three anti-TNF drugs used in inflammatory bowel disease treatment have not been compared side-by-side in clinical trials.”  Thus far in pediatrics, infliximab is the only TNF approved for clinical use; as such, the other anti-TNF agents have been used primarily when infliximab loses effectiveness.

One drawback with injectable medications has been reduced adherence; up to 50% of patients fail to maintain regular injection interval; in addition, in patients who have had intravenous infusions (rather than patients who are naive) it is preferred over injections (Jay Popp, medical director of Janssen pharmaceuticals–personal communication).

As such, when patients receive infusions (eg. infliximab), closer followup and better adherence are more likely in comparison to injections.  This certainly improves efficacy.

Related blog entries:

TNF-α antagonists and infections

Disease modifying treatment in IBD

Only one chance to make first impression

Impedance recommendations from PIG

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The ESPGHAN Pediatric Impedance Group (PIG) has published a review/consensus statement on the use of pH-Impedance monitoring (MII-pH) in children (JPGN 2012; 55: 230-34).

Conclusions from this group:

  • MII-pH provides more information than conventional pH probe.  Whether this information will “inform prognosis, or predict response to therapy in pediatric patients has yet to be determined”
  • ‘As long as there is no effective medical therapy for weakly acid and nonacid reflux, the clinical relevance of MII-pH remains debatable’
  • “There are no data on the results of antireflux surgery based solely on the detection of weakly acid and nonacid reflux”
  • MII-pH is investigational technique needing standardization before routine diagnostic use can be recommended.
  • Major indications: need to identify weakly acid and nonacid reflux, persisting symptoms during antireflux treatment, use in identifying rumination syndrome, and research
  • Limitations of MII-pH: high cost, limited contribution to change in medical care, lack of evidence-based parameters for assessment of GER

Related blog entries:

Gastroesophageal Reflux: I know it when I see it

Treating reflux does not help asthma

The Medical Pendulum and Gastroesophageal Reflux

How sensitive is Calprotectin?

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A recent article suggests that fecal calprotectin, while good, is not as good as endoscopy at detecting mucosal disease in pediatric Crohn’s disease (Inflamm Bowel Dis 2012; 18: 1493-97).

In this study, 60 consecutive children with new onset untreated Crohn’s disease (diagnosis based on Porto criteria -JPGN 2005; 41: 1-7) were enrolled in ESPGHAN growth study.  The data for this study was collected prospectively (21 investigators from multiple sites).  The calprotectin values were obtained prior to treatment.

Median fecal calprotectin values were 2198 μg/g in patients with isolated small bowel disease; this did not differ significantly from the value of 2400 μg/g in patients with colonic disease (with or without small bowel disease).

Fecal calprotectin was elevated in 95% of patients; this outperformed CRP (86%) and ESR (83%) as a marker for Crohn’s disease.  In the three children with normal calprotectin values, the serum inflammatory markers were normal in all three and two had minimal endoscopic findings.  The histology findings for these three children were not reported.

In my experience, fecal calprotectin has been very useful as a marker for Crohn’s disease and has helped identify some atypical cases by increasing my clinical suspicion.  I have had two patients with high calprotectin values who had normal-appearing mucosa with panendoscopy; they both had small bowel (jejunal) Crohn’s disease; one of these patients did have granulomas identified histologically.

While I realize that no test is perfect, I think additional studies are warranted to determine the actual sensitivity of this test for Crohn’s disease.  The sensitivity of calprotectin may yet be higher than the 95% reported in this study.

Related posts:

Biomarkers identify patients who benefit and how  Multiple additional calprotectin references with this link