Neurologic Toll of Celiac Disease

A recent prospective cohort study (M Hadjivassiliou et al. Clin Gastroenterol Hepatol 2019; 17: 2678-86) shows an alarmingly-high level of neurologic deficits in 100 consecutive adults (mean age 43 years) with a new diagnosis of celiac disease.

Key findings:

  • Gait instability in 24%
  • Persistent sensory symptoms in 12%; peripheral neuropathy was identified in 2%
  • Frequent headaches in 42%
  • Abnormal results from Brain MRI in 60%; 25% had brain white matter lesions beyond expectation for age group and 46% had abnormal MR spectroscopy of the cerebellum
  • Anti-TG6 antibodies were detected in 40% of patients and this subgroup had significant atrophy of subcortical brain regions compared to patients who were Anti-TG6 antibody-negative

Some neurologic findings improve on a gluten-free diet (GFD).  In previous studies of patients with CD and headaches, 75-80% improved or subsided after a year of strict adherence to a GFD.

My take: This study indicates that early diagnosis of celiac disease along with strict adherence to a gluten-free diet is likely to prevent permanent neurologic disability.

Related blog posts:

Improving Care Process in Celiac Disease

Previous studies have documented numerous deficiencies in the care of children with celiac disease, particularly with regard to followup.  A recent study (B Sparks et al. J Pediatr 2020; 216: 32-6) demonstrates that using a prospective patient registry can improve many aspects of care and allows scrutiny of other aspects for further improvement.

In this single center study with 25 pediatric gastroenterologists, the authors reviewed the experience in establishing their “Celiac Care Index.”

Key findings:

  • There was improved adherence: 77%–>89%
  • Improved rates of followup serology: 50–>90%
  • Improved completion of agreed-upon bloodwork: testing for ALT increased from 74% to 96%, Vitamin D from 36% to 83%, and checking hepatitis B immune status from 30% to 80%

When looking at their ‘smartset’ labs obtained in most of their 145 patients, the authors note that several may not be needed:

  • Iron: the authors state that serum iron is not needed in those who have had a ferritin and a CBC.
  • Thyroid testing: no patients had an abnormal free T4 and very few had an abnormal TSH (8 of 120 =7%).  In the subset with abnormal TSH, 5 were normal on repeat testing, 2 had previously recognized thyroiditis, and 1 had TSH elevation related to obesity.

Lab Findings:

  • Hepatitis B: 80 of 115 (70%) showed a lack of immunity to hepatitis B
  • Vitamin D (25-OH): 19 of 114 (17%) had values less than 20 ng/mL
  • ALT: 23 of 131 (18%) had values of ≥40 U/L

My take:

  1. This study shows that careful tracking of patients results in better adherence with established goals and allows for useful modifications.
  2. More long-term followup is needed –some abnormalities, like Vitamin D, may improve with treatment of the underlying disease even in the absence of vitamin D supplementation.
  3. Also, a majority of children lacked an adequate immune response to hepatitis B; testing is important to determine who needs repeat immunization.

Related blog posts:

Signage at a restaurant’s bathroom near Mount Tremblant

Disclaimer: This blog, gutsandgrowth, assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  Because of rapid advances in the medical sciences, the gutsandgrowth blog cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition

How Often Do Adults Develop Celiac Disease After Negative Testing?

RS Choung et al. Gastroenterol 2020; 158: 151-9.  

Full abstract link: (which has link to full text): “Community-Based Study of Celiac Disease Autoimmunity Progression in Adults”

Methods: In this prospective cohort study, waste blood samples from residents of a community were tested for CeD autoimmunity at 2 time points. We analyzed waste blood samples from 15,551 adults for tTGA and, if titer results were above 2 U/mL, for endomysial antibody. The median interval between the two time points was 8.8 years.


  • Of the serum samples collected at the first time point, 15,398 had negative results for tTGA, and 153 had positive results for tTGA (>4 U/mL). Based on medical records, 6 individuals received a diagnosis of celiac disease, for a cumulative incidence of celiac disease diagnosis of 0.06% over 10 years.
  • Forty-nine (0.32%) individuals with a negative result from the first serologic test for tTGA had a positive result from the second test
  • Among the 153 adults who were tTGA positive at the first time point, 31 (20%) had a subsequent diagnosis of celiac disease, 81 (53%) remained positive for tTGA without a clinical diagnosis of celiac disease, and 41 (27%) had negative test results for tTGA at the second time point.

Gluten Intake and Development of Celiac Disease -Two Studies

  • NA Lund-Blix et al. Am J Gastroenterol 2019; 114: 1299-1306.
  • K Marild et al. Am J Gastroenterol 2019; 114: 1307-14.

Thanks to Ben Gold for these references.

In the first study, the authors used an observational prospective nationwide cohort study, the Norwegian Mother and Child Cohort Study (MoBa) with 67,608 children born between 2000-2009 and with a mean followup of 11.5 years.

Key findings:

  • Celiac disease (CD) was diagnosed in 738 children (1.1%)
  • The adjusted relative risk of CD was 1.1 per standard deviation increase in daily gluten amount at age 18 months.
  • Compared to children in the lowest quartile of gluten ingestion, those in the upper quartile had an adjusted relative risk of 1.29.
  • Timing of gluten introduction, ≥6 months or before 4 months, was also an independent risk factor for CD. In those before 4 months the aRR was 1.45 and for those ≥6 months the aRR was 1.34

In the second study, the authors used the prospective Diabetes Autoimmunity Study in the Young cohort with 1875 at-risk children.

Key findings:

  • Children in the highest tertile of gluten intake between ages of 1 and 2 had a 2-fold greater hazard of developing CD autoimmunity (positive tTG antibodies) (aHR 2.17) than those in the lowest tertile.
  • The risk of CDA increased by 5% per daily gram increase in gluten intake in 1 year olds.

My take: Taken together, these studies indicate that higher gluten exposure (between 1-2 years) is associated with a modestly-higher risk of CD; in addition, early (<4 months) and late exposure (>6 months) may increase the risk as well.

Related blog posts:

Spoiler alert: This case study by A Fasano et al. NEJM 2020; 382: 180-9. describes a presentation of celiac disease and Addision’s disease. I recently had a teenager present with similar symptoms who had Addison’s alone (clues were fatigue, low sodium and hyperpigmentation)

ESPGHAN Guidelines for Diagnosing Coeliac Disease 2020

Briefly noted: S Husby et al. JPGN 2020; 70: 141-56.

Link to document: ESPGHAN Guidelines for Diagnosing Coeliac Disease 2020

Key recommendations for diagnosing celiac disease (CD):

  • If CD is suspected, measurement of total serum IgA and IgA-antibodies against transglutaminase 2 (TGA-IgA) is superior to other combinations
  • We recommend against deamidated gliadin peptide antibodies (DGP-IgG/IgA) for initial testing
  • Only if total IgA is low/undetectable, an IgG-based test is indicated
  • If TGA-IgA is ≥10 times the upper limit of normal (10× ULN) and the family agrees, the no-biopsy diagnosis may be applied, provided endomysial antibodies (EMA-IgA) will test positive in a second blood sample. HLA DQ2-/DQ8 determination and symptoms are not obligatory criteria
  • In children with positive TGA-IgA <10× ULN at least 4 biopsies from the distal duodenum and at least 1 from the bulb should be taken

Related blog posts:


P’tit Train du Nord Linear Park

Celiac Disease: “”80 percent of success is just showing up”

“80 percent of success is just showing up” —Woody Allen

Reading a recent (brief) study (BA Blansky et al. Clin Gastroenterol Hepatol 2019; 17: 2503-4) reminded me of the quote from Woody Allen.  This study of children with Celiac disease (CD) demonstrates a high rate of children who were lost to follow-up at a leading Children’s hospital.

Key findings:

  • From a randomly selected retrospective cohort (2010-2014) with 241 eligible subjects, one-fourth of children were lost to follow-up within a year of diagnosis. 22 (9%) had NO GI visits after their diagnostic procedure.
  • Risk factors for loss of follow-up: sibling with CD (HR 1.90), Medicaid insurance (HR 2.19), and older age at diagnosis; those with adherence had median age at diagnosis of 8.7 years compared with 11.4 years for those lost to follow-up.
  • Median time to tissue transglutaminase (TTG) IgA normalization was 17 months.  Of 141 who had recommended follow-up, 25% had elevated TTG IgA at last GI visit.

My take: These numbers should not be surprising to most clinicians.  If clinicians want to improve follow-up and outcomes, then families will need more nudging; EMRs can be configured to help in this task.

Related blog posts:

Quebec City

#NASPGHAN19 Selected Abstracts (Part 1)

Link to full NASPGHAN 2019 Abstracts.

Here are some abstracts that I found interesting at this year’s NASPGHAN meeting:


  1. Off-label use of topiramate may be helpful in stabilizing weight and improving NAFLD
  2. Socioeconomic barriers are frequent in NAFLD patients (the 2nd poster did not appear to show a control population):

Primary Sclerosing Cholangitis -Use of Vedolizumab for PSC did not appear to help

Eosinophilic Esophagitis

  1. EoE is four times more likely in this cohort with inflammatory bowel disease
  2. 2nd poster describes very early-onset EoE

Inflammatory Bowel Disease:

  1. Use of infliximab in VEO IBD.  Used in 46/122 (38% of patients) and 50% had persistent use 3 years later

Enteral nutrition –poster from our group describing good tolerance of plant-based formula (with Ana Ramirez).

Celiac disease.  This poster indicates low yield of additional serology for celiac disease besides TTG IgA and serum IgA. This includes testing in young patients (< 2 years) with celiac disease.