Category Archives: Pediatric Gastroenterology Intestinal Disorder

Top Lecture: Enteral Nutrition for Crohn’s Disease

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In my opinion, the best lecture from this year’s postgraduate course was from Dr. Baldassano.  Enteral nutrition in Crohn disease: Where should this be in our treatment algorithm?  Robert N. Baldassano, MD (page 115)

Dr. Baldassono has personal experience with improving with enteral therapy after failing methotrexate/remicade.  His conclusion:

Enteral Nutritional Therapy: Where should this be in our treatment algorithm?

  • Should be offered to all newly diagnosed Crohn’s patients who can tolerate Nutritional Therapy
  • Special groups (especially a good idea): Malnourished patients, Younger patients, Growth failure, History of Cancer, Family history of Lymphoma, Consider when failing other therapies

This conclusion is supported by his presentation.

Should we be immunosuppressing our Patients?  Hypothesis: IBD arises from inappropriate handling of intestinal bacteria

Elements of Modern Lifestyle Lead to Changes in Gut Microbiota

  1. Improved sanitation
  2. Less crowded living conditions
  3. Decline in parasites
  4. Vaccinations
  5. Increased antibiotic use
  6. Caesarean section
  7. Refrigeration
  8. Food processing
  9. Diet changes
  10. Improved sanitation

Diet is associated with new onset IBD

  • High dietary intakes of total fats, PUFAs, omega‐6 and meat were associated with an increased risk of CD and UC
  • High fiber and fruit intakes were associated with decreased CD risk
  • High vegetable intake was associated with decreased UC risk.  Reference: Hou JK et al. American Journal of Gastro 2011; 106:563-73
  • The Bacteroides enterotype highly associated with animal protein and saturated fats which suggests meat consumption as in a Western diet
  • The Prevotella enterotype, high values for carbohydrates and simple sugars, indicating association with a carbohydrate-based diet, more typical of agrarian societies.  References: Wu G, et al. Science. 2011 Oct 7;334(6052):105‐8

Partial or Complete Enteral Nutrition?

  • 50% vs 100% of total caloric needs for induction with elemental formula (PCDAI < 10 at 6 weeks)
  • 50% of total caloric needs 15% remission
  • 100% of total caloric needs 42% remission
  • Labs improved only in the 100% group
  • Weight gain similar in the 2 groups. References: Akobeng et al Clin Nutr 2007; Ludvigsson et al Acta Paediatr 2004;Johnson et al Gut 2006;Critch et al. JPGN: 2012 

Pediatric Longitudinal Study of Semi‐Elemental Diet and Stool Microbiome (PLEASE)

Prospective cohort study of children with Crohn disease from Philadelphia (used Peptamen), Toronto (used Modulen) and Halifax (used Osmolite); (n=90)

  • Enteral therapy with defined formula diet (n=38) vs. anti‐TNFα therapy (n=52)
  • Similar drop in PCDAI and calprotectin in TNF group and diet group. 

Other points:

  1. Insurance generally will cover nasogastric feeds
  2. Disease location –not clear that this matters with Crohn’s disease
  3. The reason EN works may be not what you are giving the patient but what the patient is not getting
  4. Bacterial populations in pediatric IBD subjects on semi‐elemental diet (16S rDNA sequencing) develop a rapid change in gut bacterial populations upon initiating diet.
  5. Partial (50%) nutrition, as noted above, helped maintain remission compared to normal diet.

Nutrition Therapy: “European” Protocol

• Induction:  Exclusive enteral nutrition with an elemental, semielemental,or polymeric formula

• Duration: 4 – 12 weeks

• Maintenance Therapy: (either)

– Nutritional therapy: Repeat 4 week cycle of exclusive enteral nutrition every 3– 4 months

OR

– Medical therapy: 6‐MP/AZA/MTX after induction with nutritional therapy

CHOP EN Experience: What if >80% of calories is from Enteral Nutrition?

  • Methods: Semi‐elemental formula, 80%‐90% of patient’s caloric needs from formula, Nocturnal NG feeds (outpatient teaching program), Normal diet as tolerated during the day
  • Duration:  7 days per week for 8‐12 weeks (induction), 5 days per week (maintenance) Reference: Gupta et al. Inflamm Bowel Dis. 2013:1374-8.
  • Induction of remission: 65% (at 8 weeks)
  • Response: 87% (at 8 weeks)
  • Significant improvement in weight and linear growth
  • Protocol is well tolerated:  no serious adverse events

Postgraduate Course Syllabus (posted with permission): PG Syllabus

Related blog posts:

Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) and specific medical management interventions should be confirmed by prescribing physician.  Application of the information in a particular situation remains the professional responsibility of the practitioner.

“Gluten-Related Disorders” (Part 2)

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Non-celiac Gluten Sensitivity NCGS -Focused discussion in Section III
  • No biologically measurable response has been found – these are people with normal celiac serology (neg ttg/ema) and normal biopsies.
  • Specific discussions regarding autism and schizophrenia.  On page 44, authors note that a 2008 Cochrane review concluded the evidence for a gluten-free diet for autism was poor.  In 2012, a two-stage RCT (Whiteley et al) of gluten-free casein-free diet reported significant group improvements after 8 and 12 months on diet. Thus, diet may be helpful.
  • Other chapters allude to NCGS as well.  Page 124: “There are no epidemiologic studies assessing the prevalence of NCGS. Bizzaro et al estimated that for every one person with CD, there are at least six to seven with gluten sensitivity.”
Wheat Allergy -Section IV
  • Forms include oral food allergy, “wheat-dependent, exercise-induced anaphylaxis,” and Baker’s asthma (aerosolized exposure).
  • Skin prick tests or RAST’s are notorious for providing a high rate of false-positive results.  Low rate of false negative results, though, are noted.

Treatment -Section VI:

  • This section provides a number of tables to assist with diet and hidden sources of gluten.
  • GFD may lead to specific nutrient deficiencies: fiber, iron, folate, niacin, zinc, vitamins B12, A, D, E, and K; also, GFD may be higher in fat.

Psychological Aspects -Section VII:

 “The family has to buy gluten-free foods and all members have to learn how to avoid contaminating gluten-free foods, dishes, toasters, and so on.” Parents have to read all food labels and prepare special meals while attending social events.
A nice sample letter is included on page 129 –should make a good EPIC smartphrase.
Difficult Cases -Section VIII:
  • Labs to check in sick CD patient (Table 2 -page 133).
  • Causes of Nonresponse to GFD: poor compliance, accidental ingestions, nonceliac disease causing symptoms.
  • While some of the authors state that true refractory disease is “rare in adults,extremely rare in children,” in other parts of the book it is noted that complete histologic response is not seen in all patients (some with apparently good adherence).

IgA deficiency (page 139).

  • 85-90% of IgA deficient patients have no clinical symptoms.  Occurs in about 1 in 300.  For those with symptoms, manifestations could include sinopulmonary disease, allergy/atopy, autoimmune diseases, giardiasis/infections, and transfusion reactions (against IgA) (see Table 8 on page 143).
  • Transiently low IgA is common in children <4 years.
  • For IgA deficient patients, risk of CD is 10-20 times general population.
  • In true deficiency, level is typically <7 mg/dL.  More often, there is a partial deficiency which is ‘almost always asymptomatic.’  In partial IgA deficiency, IgA assays identify about 90% of CD cases.
Also, in the difficult cases section an algorithm for follow-up of newly diagnosed CD is presented and discussed (page 154).  Recommendations include nutritional counseling, resource identification, family screening, and celiac education.  Consider checking iron status, vitamin D, folate, zinc, copper and DEXA.  Recommends followup serology 6 months following diagnosis and if normal, then on a yearly basis.
Related blog posts:
Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) and specific medical management interventions should be confirmed by prescribing physician.  Application of the information in a particular situation remains the professional responsibility of the practitioner.

“Gluten-Related Disorders” (Part 1)

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On the way back from our National Meeting (NASPGHAN), I had the opportunity to read “Gluten-Related Disorders” ed. by Alessio Fasano.  The book is a very good summary about the science of celiac disease (CD), wheat allergy, and nonceliac gluten sensitivity (NCGS); at the same time, there is some redundancy due to multiple authors (particularly evident in later chapters). One of the book’s features is clinical vignettes to drive home multiple teaching points.  For example, the ‘refractory’ CD patient who in fact has Crohn’s disease. The book also provides a code to obtain the information online, so it is fully searchable.  In the introduction, there is an in-depth explanation of why gluten can be so difficult for the GI tract.  The discovery that a gluten-free diet can be helpful was a byproduct of wheat shortages during WWII.  Here are some useful insights that were noteworthy:

Definitions (page 9):  reviews the terms “silent CD,” “potential CD,” and “latent CD.”

  • Silent =asymptomatic but with all other features: +antibodies, +HLA type, +abnl histology
  • Potential =+antibodies but lack of histology evidence  (antibodies often precede development of clinical disease)
  • Latent =previous evidence of CD but currently tolerating gluten in diet with normal histology

Epidemiology:

  • While increase in CD is partly due to awareness, there has been a “true increase in prevalence, with rates doubling every 20 years or so.”
  • Early vaccinations are not risk factors for the development of CD
  • Breastfeeding can reduce risk of CD by about 50% though gluten should be introduced between 4-6 months.

Presentation:

  • Table of the main extraintestinal manifestations on page 24.  Most common: anemia (especially iron deficiency), short stature, and pubertal delay.
  • Associated diseases (Table 3, page 29): Down syndrome, Turner syndrome, Type I Diabetes, Williams syndrome, IgA deficiency, and Autoimmune thyroid disease.
  • Eosinophilic esophagitis has been identified in a small number of patients with celiac disease.  The book notes a study with 7 pediatric patients; only one of them improved their esophageal eosinophilia with a GFD.

Tips on diagnosing celiac

  • Bulb abnormalities with a normal 2nd portion of duodenum biopsy can be seen in 10% or more of patients with celiac.  The authors recommend obtaining 4 biopsies from 2nd and 3rd portion and 2 biopsies from bulb (separate containers) (page 144-145).
  • Most celiac experts say there is no celiac without DQ2 or DQ8.  There are several situations in which a negative HLA type could be helpful (page 78)
  1. -negative serology but abnormal histology
  2. -gluten-free diet (GFD) started before diagnosis confirmed
  3. -failure to respond to GFD
  4. -asymptomatic high-risk individuals to help determine if periodic serology is worthwhile
  • In most individuals, obtaining TTG IgA along with serum IgA is recommended for diagnosis (and avoiding older gliadin antibody tests).  If clinical suspicion is high, endoscopy is warranted regardless of result.
  • Under the age of 2, deamidated anti-gliadin antibodies appear months earlier than the TTG in prospective studies, so order the dAGA IgG and dAGA IgA in kids under 2. (Available with both quest and labcorp).  The deamindated anti-gliadin antibodies may be more helpful/sensitive in monitoring dietary adherence than TTG.
  • Infants who have a first degree family member with celiac should be introduced to “small” amounts of gluten between 4 and 6 mos of age – not before and not delayed.  It appears to promote tolerance though it’s not clear if it just delays inevitable onset.  Small amounts can be a serving a day of a mixed, barley baby cereal.
  • Section V is devoted to diagnosis.  Table 1 (page 72) lists the sensitivity/specificity of the available serologies.
  • Screening asymptomatic persons.  The controversy regarding this practice is alluded to on page 75.  Currently NASPGHAN recommends screening at risk groups whereas AGA does not.
  • Endoscopy/Biopsy discussed (pages 78-82).  States a biopsy is not needed in the case of dermatitis herpetiformis due to characteristic deposits of IgA in the dermal papilla.  The authors recommend biopsy in all cases, but review ESPGHAN guidelines which state that biopsy can be omitted if TTG IgA >10 time ULN –if verified by positive EMA, HLA typing, and followed for symptomatic improvement.
  • Antibody tests “become negative in 15% after 1 month on GFD and in 57% after 3 months…diagnosis of CD cannot be made while on GFD.”  Algorithm for diagnosis of CD with a child on GFD presented on page 148.
Related blog links:

Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) and specific medical management interventions should be confirmed by prescribing physician.  Application of the information in a particular situation remains the professional responsibility of the practitioner.

Nexium versus Fluticasone for EoE

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As noted in previous blog posts (EoE: Drugs, Diets, Dilatation and PPI-REE | gutsandgrowth, EoE –Journal Club (Part 1) | gutsandgrowth, and EoE –Journal Club (Part 2) | gutsandgrowth), proton pump inhibitors are recommended as 1st line therapy in suspected eosinophilic esophagitis (EoE) for several reasons.  Besides the potential for gastroesophageal reflux to cause esophageal eosinophilia, there has been recognition of PPI-responsive eosinophilic esophagitis (PPI-REE).  In adults, the response to proton pump inhibitors, both clinically and histologically, is likely higher than in children; nevertheless, in children it is anticipated that 20-40% of patients with suspected EoE will have a histological remission with PPI therapy.

A recent study in adults suggests that PPIs may in fact outperform topical steroids (Am J Gastroenterol 2013; 108: 366-72).  Thanks to Ben Gold and Seth Marcus for identifying this reference.  This study enrolled 42 patients: 90% male, 81% white, mean age 38 years. It was a prospective single-blinded, randomized controlled trial with newly suspected EoE; half of the patients received esomeprazole 40 mg daily and half fluticasone swallowed aerosol 440 mcg twice a day.  After 8 weeks, all patients had repeat endoscopy; a total of eight biopsies were obtained –four at two locations: 15 cm above LES and 3 cm above LES.  In addition, at the start of the study, patients also underwent 24-h pH/impedance monitoring.  4 of the 21 patients in each group had abnormal degrees of gastroesophageal reflux/gastroesophageal reflux disease (GERD).

Study characteristics note that 62% of patients had coexisting atopic disorders.

Results:

  • There was no significant difference in esophageal eosinophilia response with 19% of the fluticasone and 33% of the esomeprazole achieving an eosinophil count < 5/hpf (P=0.484)
  • In patients with coexisting GERD, all 4 esomeprazole patients achieved histologic remission  compared with none of the fluticasone-treated patients.
  • When the GERD patients were excluded, the histological remission was quite similar: 24% with fluticasone and 18% for esomeprazole.

Overall, this study population had a lower rate of response to topical steroids than in multiple previous studies.  More typically, response rates of ~50% have been reported; however, studies have shown lower responses in some adult studies.  Variability in response could be related to multiple factors included dosage, duration, delivery, and definition of response.  In addition, population characteristics included disease duration and frequency of underlying atopic disease and GERD play a role.

Take-home points: Although this is a small study, it reinforces the fact that PPIs induce a histological response and clinical response in some patients suspected of having EoE regardless of whether GERD is present.  PPIs are considered 1st line therapy.  Topical fluticasone had a lower response rate in this study.  However, in clinical pediatric practice, topical steroids are effective in about 50% of patients.

Additional related blog entries:

Crohn’s Research: Going to Pot

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A recent pilot study using Cannabis for Crohn’s disease is certain to attract a lot of attention (Clin Gastroenterol Hepatol 2013; 11: 1276-80).  The side effects are definitely less frightening than many of the accepted treatments.

Background: Cannabis has a long record of medicinal uses; it contains more than 60 different compounds, though Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are thought to be the most active.  Cannabis has known antiinflammatory properties and has been shown to reduce colitis in a mouse model.

Study design/characteristics: 21 of 51 screened patients participated; these patients had active Crohn’s disease despite thiopurines in 20  or 21 and anti-tumor necrosis factor (TNF) therapy in 18.  These 21 patients were enrolled in a double-blind, placebo-controlled study.  The average age in the cannabis group was 46 years compared with 37 in the placebo group.  Both groups received cigarettes twice daily; the cannabis cigarettes had 115 mg of THC whereas the placebo group had cannabis flowers in which the THC had been extracted.  Though this was a double-blind study and efforts were made to mask the psychotropic effects by recruiting patients naive to cannabis, nevertheless, by the end of the study most of the patients knew whether they were in the active group or the placebo group.

Results:

  • Cannabis group had a 45% remission rate (5 of 11) with a CDAI of ≤150; the placebo group had a 10% remission rate.  This did not achieve statistical significance.
  • The response rate (CDAI drop of >100) was noted in 90% (10 of 11) of cannabis group compared with 40% in the placebo group.
  • The mean CDAI reduction was 177 in the study group compared with 66 in the placebo group (P= .005).
  • There were no significant laboratory changes (eg. Hgb, CRP, LFTs, kidney function).
  • No significant side effects were noted.  The study group reported less pain, improved appetite, and better satisfaction with their treatment.

In their discussion, the authors note that this is a small study.  They chose the smoking route with THC-rich cannabis to achieve higher blood levels, but note that oral dosing may be effective.  The 8-week duration of the study and lack of more objective markers of response precludes firm conclusions.

Take-home message: Cannabis should be studied further for its potential role in controlling inflammation.  This study’s timing will increase the broader interest in medical marijuana applications.

Related links:

Thiopurines = Low Efficacy for Crohn’s

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The enthusiasm for thiopurine therapy for Crohn’s disease (CD) had already dropped a lot before two pivotal articles were recently published that confirmed the modest efficacy:

  • Cosnes J, et al. Gastroenterol 2013; 145: 758-65
  • Panes J, et al. Gastroenterol 2013; 145: 766-74
  • Gastroenterol 2013; 145: 714-16 (editorial)

The Cosnes study (from the GETAID group) reports an open-label randomized trial in 147 adult patients with newly diagnosed CD (from 2005–>2010) and risk factors for disabling disease who were recruited from 24 French centers.  Risk factors for disabling disease:

  • Age <40 years
  • Active perianal lesions
  • Corticosteroid use within 3 months of diagnosis

The characteristics and Paris classification are detailed in the paper’s Table 1. Patients were divided into early azathioprine or “conventional” treatment. Patient’s were followed for 3 years.  Azathioprine was dosed at 2.5 mg/kg/day.  The primary endpoint was the proportion of trimesters spent in corticosteroid-free and anti-tumor necrosis factor (TNF)-free remission.

Results:

  • 67% of azathioprine group achieved the primary endpoint compared with 56% in the conventional group.  The difference in achieving the primary endpoint was not statistically significant between the two groups.  Also, 41 (61%) of the conventional group were placed on azathioprine (mean time 11 months after enrollment).
  • The azathioprine group patients were more likely to not have perianal surgery (96%) compared with the conventional group patients (82%).
  • Adverse events included pancreatitis in 7 (10%) of azathioprine group compared with 1 (1%) of conventional group.  Elevated liver function tests were noted in 3 (4%) compared with 1 (1%) respectively.  No cases of neutropenia were noted in early azathioprine group.

The latter finding is interesting especially as the authors did not check thiopurine methyltransferase (TPMT) assays in a systematic manner.

Panes et al (for the AZTEC study group) performed a prospective double-blind trial of adult patients with a recent CD diagnosis (<8 weeks).  This study enrolled 131 patients from 31 centers in Spain.  68 received azathioprine (2.5 mg/kg/day) and 63 received placebo.

Results:

  • After 76 weeks of treatment, 30 (44.1%) azathioprine patients and 23 (36.5%) placebo-treated patients were in sustained corticosteroid-free remission (P= .48).
  • Relapse rates were lower in azathioprine group compared with placebo: 11.8% vs 30.2%.
  • Serious adverse effects were more frequent in the azathioprine group compared with placebo: 20.6% vs. 11.1% (P= .16).  In the azathioprine group, 7 (10%) developed pancreatitis, 16 (24%) developed leukopenia, 9 (13%) developed anemia, and 9 (13%) developed abnormal liver function tests.  Infections were more common in the placebo-treated group (24%) compared with 12% in the azathioprine group

The accompanying editorial should be mandatory reading for all health care providers who help manage inflammatory bowel disease (IBD) patients.  The editorial traces how thiopurines (azathioprine and 6-mercaptopurine) became an accepted cornerstone of IBD treatment.  In adults, after initial disappointing results from Summers et al (Gastroenterol 1979; 77: 847-69), efficacy was demonstrated in a seminal study by Present et al (NEJM 1980; 302: 981-87).  However, the authors note that a recent Cochrane review reported that “thiopurines are not effective for induction of remission, but are effective for maintenance of remission.”

The editorial notes that a high degree of efficacy was demonstrated from a small but influential pediatric study of 55 patients.  After a high remission rate (89%) for all patients, this study showed that among those in remission, “1 patient (4%) in the 6MP group had a relapse within 180 days of achieving remission, compared with 7 patients (28%) in the placebo group.”

The editorial draws the following conclusions from the current studies:

  • “The remaining indications for primary therapy with thiopurines are maintenance of steroid-induced remission/steroid sparing in patients with CD that is not newly diagnosed, and prevention of postoperative recurrence.”
  • “The strongest indication for thiopurines may be as part of combination therapy.”
  • “If TNF antagonists had a similar low cost as generic thiopurines, there would likely be little debate regarding an evolution toward treatment of CD with TNF antagonists, either as monotherapy or ideally as combination therapy.  Currently, the annual costs of TNF antagonists is 10-20 times that of thiopurines.”
  • Because of the difference in cost.., “the use of thiopurines in CD is likely to persist, despite the shrinking number of indications, the modest effect size, and the suboptimal safety profile.”

Related blog posts:

Review of Button Batteries

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A recent open access article reviews button batteries and reiterates algorithm from poison control (noted in previous blog post: Button Battery Algorithm Link | gutsandgrowth).  This article has some excellent figures detailing the extent of the problem and has relevant pictures of radiographs and mucosal damage.

Here’s the reference:

International Journal of Pediatric Otorhinolaryngology 77 (2013) 1392–1399

Here’s the link:

http://authors.elsevier.com/offprints/PEDOT6686/7551db6b14c8aabfa827016d69367c08 …

Precise Identification of C difficile Transmission

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A recent study uncovers some useful information about C difficile by using whole-genome sequencing on 1250 separate C difficile cases (NEJM 2013; 369: 1195-205).

Between 2007-2011, the authors used genetic sequencing to determine the similarity of C difficile cases.  They were able to successfully sequence 1223 (98%) of the identified cases.  Of these isolates, 71% were from inpatients, 25% from outpatients, and 4% from patients at other hospitals. To determine similarity, they compared single-nucleotide variants (SNVs) between the isolates.  If isolates were related, it was anticipated that there would be 0 to 2 SNVs between transmitted isolates (95% prediction if less than 124 days apart).

This study was from the Oxford University Hospitals which provide all acute care and 90% of hospital services in Oxfordshire, United Kingdom (~600,000 population).

Results:

  • Only 35% of cases were genetically related to at least one previous case.
  • Of the 333 (35%) with ≤2 SNVs (consistent with transmission), and 126 (38%) had close hospital contact with another patient, 120 (36%) had no hospital or community contact with another patient.
  • 13% of cases were genetically related (≤2 SNVs) but without any evidence of plausible contact.
  • 45% of C difficile cases were genetically distinct (>10 SNVs from any previous case) from all previous cases.  This indicates that the source of the infection was not from another symptomatic case; most likely these cases were acquired from asymptomatic persons or an environmental reservoir.
  • There were reductions in the rate of C difficile infection during the 4-year study.  The authors relate this to changes in antibiotic prescribing behavior, specifically the restriction of fluoroquinolones and cephalosporins.

Aspects of the setting may limit some of the conclusions.  For example, the study was conducted in a nonoutbreak setting and the hospitals had established measures to limit transmission from symptomatic patients.  These included the following:

  • isolation of patients with suspected C difficile
  • daily hypochlorite disinfection
  • monitoring of compliance

These measures will decrease nosocomial transmission.  However, at the same time, some of the genetically distinct cases could still have been acquired in the hospital setting from asymptomatic hospital sources. While the authors concede a number of limitations, this study is quite helpful in understanding the role of hospitals in controlling C difficile infection.

Take-home message: the fact that only 35% of cases were related to other symptomatic cases indicates that hospital control measures by themselves will not be effective.  The most important aspect in reducing C difficile infection will be optimizing antibiotic usage.

Related news media: On the same day of that I read this study, there was an article in the Atlanta Journal Constitution (“PLEASE wash your hands … Please.”) which describes a first-hand account of C difficile infection which contributed to a slow recovery from intestinal surgery.  The article contained some questionable assertions including that C difficile was “impossible to eradicate” and that her immune system trapped C difficile in peritoneal abscesses which required drainage (these abscesses were more likely related to the initial operation). However, the article is a stark reminder that many hospital staff do not follow basic hand washing recommendations.  The article is really bad PR for the named hospital.

Related blog posts:

Mitochondrial Liver Disease

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A recent review provides advice for the evaluation of the child with suspected mitochondrial liver disease (JPGN 2013; 57: 269-79).

Clinical presentations:

  • Acute in a child with no history of hepatic dysfunction
  • Chronic liver and CNS dysfunction
  • Onset of liver disease in patient with known CNS disorder

Suggested Tiered Diagnostic Evaluation: Table 1 provides extensive suggestions.

  • 1st tier: CMP, INR, AFP, CPK, Phos, CBC/d, ammonia, Lactate/pyruvate (preferably 1 hour after feeding), serum ketone bodies, serum acylcarnitine profile, carnitine profile, urine organic acids, serum amino acids, urine acylglycines and 2-ethylmalonic acid quantification, plasma thymidine (especially if intestinal dysmotility), quantitative serum methylmalonic acid, CSF analysis (lactate and pyruvate, amino acids, protein)
  • 2nd tier: genotyping for more common genes (eg. panel with POLG1, DGUOK, MPV17), other genetic tests based on tier 1 testing (see table for details)
  • 3rd tier: liver biopsy, skin biopsy, and muscle biopsy (see table for details)
  • 4th tier: additional genetic tests based on 1st three tiers

Table 2 describes potential evaluations in other organs.  For example, for brain, MRI, EEG and CSF.

Table 3 lists ~27 mutation/syndromes and clinical features.

The last three words from the conclusion of the publication are not supported by the review.  The authors state that this systematic approach “can aid in making a timely, accurate, and cost-effective diagnosis.”  While the authors do not provide estimates of the expense of these tests, they are probably very expensive, though less costly than a failed liver transplantation.

Bottomline: “Available technology to aid in diagnosis has improved substantially.  Nonetheless, diagnosis of suspected mitochondrial disease in children is complicated.”

Related blog post:

Proven treatments for mitochondrial disorders | gutsandgrowth

NASPGHAN Preview

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I had a few free minutes so I decided to take a look at a bunch of upcoming lectures from the 2013 NASPGHAN upcoming meeting.  With electronic media, it is easy to take a quick glance.  Here’s the master link to all of the following talks:

Annual Meeting page.

Some of the power point lectures that I’ve seen so far:

  • Is my PPI dangerous for me? Eric Hassall MBChB, University of British Columbia One point in his slides that I had not seen much about was a hypothesis that PPI use may predispose to the development of eosinophilic esophagitis by allowing food proteins to be more intact ( attributed to Merwat, Spechler. Am J Gastro ’09).  He explains that “acid reflux” is a clever marketing term and has a slide with Madmen actors.  If there is “acid,” one must need acid suppression.
  • My child doesn’t go to school Lynne Walker MD, Vanderbilt University.  Lynne shows an interesting fax from a parent that asks if the problem is physical, how will she help? And, if it is psychological, how can this be remedied?  She outlines a lot of pain theory and indicates that parents need to become health coaches, avoid catastrophizing (?spelling), and encourages mental health evaluation.  Use the parents words ‘I’m going to refer xxx for relaxation and stress management.’
  • My child’s H. pylori will not go away – (the resistant bug) Benjamin Gold MD, Children’s Center for Digestive Healthcare. Ben manages to stuff so much information into his talk.  His talk is like one of those clown cars where more and more people keep coming out.  He has slides with worldwide resistance maps, slides with treatment regimens and algorithms, and the reasons for treatment failure. Perhaps I can convince him to give a live preview.
  • Administrative/executive functioning Richard Colletti MD, Fletcher Allen Healthcare. Offers personal and pragmatic advice for career advancement.  His slides indicate that he started his GI fellowship at age 40.  One of his quotes, “80% of success is showing up” (Woody Allen) is definitely true.  It’s pretty much akin to what I learned about success in medical school.  You need the three As: availability, affability, and ability.  My mentor said the first was what people needed most.
  • The changing face of intestinal transplantation
    Simon Horslen MD, Seattle Children’s Hospital.  Lecture notes that number of intestinal transplants have decreased dramatically, particularly in children. In 2012, only about 100 intestinal transplants were performed whereas it had peaked at nearly 200.  Much of the credit is due to intestinal rehabilitation work and adjustments in parenteral nutrition (eg. lipid minimization, line care).  Two most common reasons for intestinal transplantation at this time are gastroschisis and volvulus.
  •  Gluten sensitivity: Fact or fiction Alessio Fasano MD, MassGeneral Hospital for Children. This blog has covered a lot of the same material, but Alessio’s slides are pretty impressive.  Also, I was not aware that Lady Gaga consumes a gluten-free diet
  • Controversies in parenteral nutrition Christopher Duggan MD, Boston Children’s Hospital.  This lecture provides a timely update on nutrient deficiencies due to component shortages and discusses lipid minimization compared with fish oil-based lipid emulsions.
  • Vitamin D and immunity James Heubi MD, Cincinnati Children’s Hospital and Medical Center.  In the beginning of the slides, Jim provides a very user-friendly definition of an expert and a suitable picture.  He indicates that in 2011 there were 3746 vitamin D publications but inexplicably only chooses to review a tiny fraction.

At the time of this posting, I haven’t had a chance to look through these talks: