“When is Celiac Disease Celiac Disease?”

A recent study (R Auricchio et al. Gastroenterol 2019; 157: 413-20, and editorial PR Green S Guandalini, pg 293-4) provides insight into the topic of “potential celiac disease.”

It is difficult trying to explain the concept of potential celiac disease (CD) to families.  Potential CD refers to the situation of having positive celiac serology but normal duodenal mucosa. In this study, the authors prospectively followed 280 children (age 2-18 yrs) with 2 consecutive abnormal serological tests (anit-TG2, EMA) along with normal duodenal architecture who continued a diet containing gluten.

Key findings:

  • 42 (15%) developed villous atrophy at median followup of 60 months
  • 89 (32%) became serologically-negative for CD
  • Cumulative incidence of progression to villous atrophy was 43% at 12 years.
  • The strongest predictive factor for villous atrophy was age: 7% of children less than 3 years developed flat mucosa, compared with 51% for age 3-10 and 55% for those older than 10 years

Advice on potential CD from editorial –titled “When is Celiac Disease Celiac Disease?”

  • Review the biopsies: were there adequate biopsy specimens? ≥4 from descending duodenum and ≥1 from duodenal bulb
  • Have a second specialist pathologist review specimens
  • If a patient with potential CD is symptomatic, institute a gluten-free diet and then follow for clinical and serologic response
  • If asymptomatic, “a wait and see approach is appropriate with interval biopsies every 2 years, if the elevated antibodies persist”

The editorial also note that none of the patients in this cohort would have been mislabeled with a diagnosis of CD using the non-biopsy approach as none of them had tTG antibodies >10 times the upper level of normal.

My take: This useful study should help with counseling parents about the likelihood of developing celiac disease in those with the “potential” label.  Younger children (<3 yrs), compared to older children, are less likely to convert from potential celiac disease to actual celiac disease..

Related blog posts:

Crater Lake, OR

Reliability of High Serology in Asymptomatic Celiac Disease

Another study (SP Paul et al. JPGN 2018; 66: 641-44) has shown that high anti-TTG IgA levels are reliable in establishing the diagnosis of celiac disease in asymptomatic children from high-risk groups. In this study with prospectively-collected data from 2007-2017, 84 of 157 children had anti-TTG titers >10x ULN.  75 of these 84 were from high-risk groups, mainly type 1 diabetes (36), and first degree relatives (24)

Key finding:

  • All 75 with high titers from high-risk groups had histologic evidence of celiac disease.

Related blog posts:

Related studyR Mandile et al. JPGN 2018; 66: 654-56. This prospective study showed that 19 of 35 (54%) patients with potential celiac disease had a complete clinical response on a gluten-free diet to symptoms like abdominal pain and diarrhea.  Thus, in many patients with potential celiac disease, a gluten-free diet will not be effective.

Related blog posts:

 

Will Asymptomatic Patients with “Potential” Celiac Disease Benefit from a Gluten-free Diet?

A recent study (Volta et al. Clin Gastroenterol Hepatol 2016; 14: 686-93) indicates that those with “potential” celiac disease, who are asymptomatic, are unlikely to benefit from a gluten-free diet.  A useful summary is available on the AGA blog: What Happens to Patients with Markers of Celiac Disease but No Symptoms?

An excerpt:

Celiac disease is an immune-mediated gluten-dependent systemic disorder characterized by serologic and genetic factors and villous atrophy in the small intestine. Although some people test positive for antibodies and carry genetic alleles associated with celiac disease, they have relatively normal or slightly inflamed intestinal mucosa, with no or mild enteropathy. These patients are considered to have potential celiac disease (defined as increased serum levels of antibodies against tissue transglutaminase [tTG] without villous atrophy). They can have gastrointestinal and extra-intestinal symptoms or be completely asymptomatic…

To learn more about progression of potential celiac disease, Umberto Volta et al performed a prospective study to track clinical, serologic, and histologic features of 77 patients. The subjects had normal or slight inflammation of the small intestinal mucosa and were followed for 3 years.

Sixty-one patients had intestinal and extra-intestinal symptoms and 16 were completely asymptomatic at diagnosis…

Gluten withdrawal led to significant clinical improvement in all 61 symptomatic patients.

Of the 16 asymptomatic patients, who were left on the gluten-containing diets, only 1 developed mucosal flattening; levels of anti-endomysial and tTG antibodies fluctuated in 5 of these patients or became undetectable.

My take: In symptomatic patients (but not asymptomatic patients) with potential Celiac disease, a gluten-free diet may be worthwhile.

Related blog posts:

Mina Falls, El Junque

Mina Falls, El Junque

“Gluten-Related Disorders” (Part 1)

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.