Tag Archives: celiac disease diagnosis

gluten challenge

Hope for a Less Challenging “Gluten Challenge”

The current “gold standard” tests for celiac disease include testing for celiac antibodies in patients’ blood and performing an endoscopy to obtain small bowel biopsies. In order for these tests to be accurate, one has to be eating gluten up until the time of testing.  If a patient is already on the gluten-free diet when these tests are done, the diagnosis of celiac disease can easily be missed.

Since starting this page I’ve encountered many people who have decided that they’d like to be tested for celiac disease after starting on the gluten-free diet.  Per the celiac disease experts, a “gluten challenge” must be performed in these cases to assist in the diagnosis of celiac disease. A gluten challenge requires eating foods containing gluten for a prescribed period of time prior to an endoscopy and/or blood testing for celiac disease. The length of time and amount of gluten that need to be consumed for a gluten challenge vary from source to source. Here are some examples of different recommendations for a gluten challenge (current as of July 5, 2014):

University of Chicago Celiac Disease Center: “For a gluten challenge we recommend eating 1/2 slice of bread or a cracker each day for the duration of the challenge. Prior to blood testing we recommend 12 weeks of eating gluten. Prior to an endoscopic biopsy we recommend 2 weeks of eating gluten. In the case of a severe reaction to gluten, a medical professional may opt to shorten the 12-week challenge and move immediately to an endoscopic biopsy.”

Celiac Disease Center at Columbia University: “In individuals who are willing to further pursue the question of whether they have celiac disease, we will advise a gluten challenge. This consists of ingesting at least 4 slices of bread a day for one to three months followed by an endoscopy and biopsy. There is no evidence that following antibody tests is beneficial in establishing a diagnosis of celiac disease because these tests are not sensitive in this setting.”

Celiac Disease Center at Beth Israel Deaconess Medical Center: “Gluten is reintroduced into the diet and after a period of time (ideally 6 to 8 weeks if the challenge can be tolerated for that long) blood tests and an intestinal biopsy are performed. If the gluten challenge is not tolerable for the full 8-week period blood tests and biopsy can be performed sooner but this can lead to a false negative result.”

In addition, Dr. Leffler and colleagues published a paper in 2013 showing that the majority of patients with celiac disease will test positive after eating >3g gluten/day for 2 weeks. A typical piece of wheat bread contains about 5g of gluten.

Despite all of the confusion, there is hope on the horizon for a shorter gluten challenge in the future.  Researchers at the Walter and Eliza Hall Institute in Australia have been developing a blood test that measures gluten-reactive T cells, immune cells that increase in response to gluten in those with celiac disease, via cytokine release assays.  In a pilot study published earlier this year, patients with celiac disease had a significant jump in blood levels of gluten-responsive T cells, compared to controls, after only 3 days of consuming gluten. Per Dr. Jason Tye-Din, one of the researchers working on this test, “We hope that larger studies can validate these findings and establish its role in the diagnosis of celiac disease.” For the sake of my gluten-light kids, and everyone else who is in a similar situation in regards to diagnosis, I hope he is right.

A press release regarding the study can be found here.

Out of curiosity, have any of you been diagnosed with celiac after doing a gluten challenge? If so, do you remember how much gluten you had to eat and for how long prior to testing?

Full reference:

Ontiveros NTye-Din JAHardy MYAnderson RP. Ex-vivo whole blood secretion of interferon (IFN)-γ and IFN-γ-inducible protein-10 measured by enzyme-linked immunosorbent assay are as sensitive as IFN-γ enzyme-linked immunospot for the detection of gluten-reactive T cells in human leucocyte antigen (HLA)-DQ2·5(+) -associated coeliac disease. Clin Exp Immunol. 2014 Feb;175(2):305-15.

 

ID-100260936

Updated Guidelines on the Diagnosis and Management of Adult Celiac Disease

I tried to abstain from reviewing celiac disease research for my 10 day vacation to Massachusetts and failed (proving that I am a big nerd). Earlier today when I checked out Pubmed.gov I came across a June 10th publication entitled “Diagnosis and management of adult coeliac disease: guidelines from the British Society of Gastroenterology.” This paper summarizes recommendations and information from a panel of 21 worldwide celiac disease experts.  You can find the entire article here. If you have the time, the entire article is worth reading.

As I read I learned some new facts, figures, and celiac disease information:

6-22% of cases of celiac disease are seronegative. This means that between 6-22% of people with celiac disease do not have abnormally high antibodies on celiac blood screening tests but do have abnormal small intestinal tissue on biopsy.

First degree family members of celiacs (parents, siblings, and children) have a 16-fold increased risk of also developing celiac disease if they are HLA-DQ2 positive on celiac gene testing.

If a patient has abnormally high celiac disease antibodies, but a normal small bowel biopsy when endoscopy is done (no signs of celiac), then some of the experts recommend that endoscopy be repeated so that jejunal biopsies can be performed. The jejunum is the 2nd portion of the small intestine and is not normally biopsied when a patient is evaluated for celiac disease.  Video capsule endoscopy can also be used in equivocal cases.

Biopsy reports should include all of the following (this is a bit technical but important for those of us who have copies of our own reports, and/or our family members’):

  • Number of biopsies (including those from the duodenal bulb) and orientation.
  • The architectural features (normal, partial, sub-total or total villous atrophy).
  • Comment on the content of the lamina propria (in CD these are lymphocytes, plasma cells and eosinophils, and occasionally neutrophils, but cryptitis and crypt abscesses should suggest other pathology).
  • Presence of Brunner’s glands.
  • Presence of crypt hyperplasia, villous height: crypt depth ratio (3:1).112 The absence of plasma cells suggests common variable immunodeficiency.
  • Evaluation of IELs (with immunocytochemical staining for T cells (CD3) in equivocal cases) is vital.

After diagnosis with celiac disease, adults should be followed-up annually with all of the following: complete blood count, ferritin, folate, Vitamin B12, calcium and alkaline phosphatase levels, thyroid function testing and glucose levels, liver function tests, and celiac antibody levels. In the absence of symptoms, having a follow-up biopsy appears to be controversial. Most of the experts recommended that it be done between 2 and 5 years after diagnosis. 6 months after diagnosis definitely appears to be too soon.

In regards to a gluten challenge, the authors stated: “To perform a gluten challenge, a recent study recommends a 14-day gluten intake at ≥3 g of gluten/day (two slices of wheat bread per day) to induce histological and serological changes in the majority of adults with CD. The challenge can be prolonged to 8 weeks if serology remains negative at 2 weeks.”

In conclusion, this paper is a comprehensive overview of the latest and greatest in regards to celiac disease in adults.  Now that I’ve discussed it I am going to return to my vacation! Hope that you’re all having a good summer thus far. Please let me know if you come across any interesting articles, research, etc.

Reference:

Ludvigsson J, Bai J, Biagi F, Card TR, Ciacci C, Ciclitira PJ, Green P, Hadjivassiliou M, Holdoway A, van Heel DA, Kaukinen K, Leffler DA, Leonard JN, Lundin KE, McGough N, Davidson M, Murray JA, Swift GL, Walker MM, Zingone F, Sanders DS; Authors of the BSG Coeliac Disease Guidelines Development Group. Diagnosis and management of adult coeliac disease: guidelines from the British Society of Gastroenterology. Gut. 2014 Jun 10. pii: gutjnl-2013-306578. doi: 10.1136/gutjnl-2013-306578. [Epub ahead of print]

 

The Scope is Clear (At Least for Now)

clairebear1

Claire is the youngest of our four children and was the first born after my diagnosis with celiac disease. She was a very healthy baby and I can’t recall her having any health issues during her infancy other than one or two mild colds and a touch of constipation.  Then, when she was about a 13 months old she began to have very high fevers, up to 104.5-105 F, that would come out of the blue and last between 2 and 5 days.  During these fevers she would have no other signs or symptoms of infection (i.e. rashes, vomiting, cough), she looked good, and, for the most part, her blood and other lab tests were normal. She had 9 or 10 total episodes of fever without a source during her 2nd year of life. Celiac disease was always in the back of my mind but I could not link her fevers with eating gluten. Although our home is 100% gluten-free, my kids do eat gluten outside of the home, in part so that I can keep tabs on whether or not they develop symptoms after eating it.

Claire’s fevers stopped in December, only to be replaced by episodes of diarrhea. Her poop was tested for bacteria, parasites, white blood cells, and all kinds of other good stuff.  I opted out of blood screening labs for celiac disease at this point as 1.) The celiac antibody panels are not often reliable in her age group, especially in kids who are “gluten-light” at baseline like Claire was, 2.) I couldn’t bear the thought of making her go through any more blood draws after all the times she’d had to be poked for her fevers, and 3.) I did not want her to have to go through a gluten challenge to get a reliable small bowel biopsy via endoscopy (since she was eating such small amounts of gluten at baseline). Our gut instinct was that her system was reacting to something in her diet. So, we put her on a gluten-free and milk-free diet in January, started her on a high-potency probiotic, and, her poops become normal and the fevers did not return.

Our oldest daughter had a milk protein allergy during infancy, so I prayed that Claire’s symptoms were from a milk protein intolerance of some sort, as most kids outgrow this. However,  when we re-introduced milk, none of Claire’s symptoms returned. But when she accidentally ate gluten the diarrhea and abdominal bloating returned on 2 separate occasions.  And then, when we let her eat a non-GF chicken nugget in April on purpose, both the diarrhea and fever returned with a vengeance.

Although I wanted to be able to keep Claire gluten-free forever, I knew that it was time for her to be formally evaluated for celiac disease.  As a doctor, I feel very uncomfortable trying to diagnose my own kids with anything. It seemed that she was sensitive to gluten, but in order to diagnose a child with non-celiac gluten sensitivity, I knew that celiac disease needs to be ruled out.

We met with a pediatric gastroenterologist named Dr. N who is affiliated with a very well-respected tertiary children’s hospital. Dr. N was phenomenal and very knowledgeable about celiac disease. He assured me that he would take enough duodenal biopsy samples (at least 5) and that he would include the duodenal bulb (in some cases, this is the only part of the small intestine where the damage from celiac can be found). He agreed that even if Claire’s small bowel biopsy showed only Marsh 1 damage (mildest findings seen in celiac disease) that he would give her a celiac diagnosis based on her symptoms and family history. We began to give Claire foods with gluten to eat, and for weeks she enjoyed non-GF pizza, Oreos, ice cream with cereal bits on top, and all kinds of other treats that she does not normally eat. Interestingly enough, she did not develop diarrhea but instead became mega-constipated. She did not develop a fever. I almost cancelled the biopsy at this point but decided to go through with it as Dr. N. said that he’d seen this happen with previous gluten challenges in kids who ended up having celiac disease.

Claire could only have clear liquids on the morning of the scope, so all four of our kiddos drank white grape juice and ate yellow jello and popsicles for breakfast. I let her watch Frozen during the 2 hour drive to the hospital. Claire was in great hands with the nurses, anesthesiologist, and other staff who we met at the children’s hospital on the morning of her endoscopy. She was given a medication called Versed which made her sleepy and 20 minutes later they wheeled her away to the O.R. The entire procedure took 15 to 20 minutes and we were reunited about half an hour later when she woke up.  She was a bit cranky at this point, much like she would have been if we woke her from a deep sleep at home, but soon after she was drinking juice and eating peanut butter out of little individual cups with a spoon.  She then ate a huge bowl of GF mac and cheese followed by about 8 cookies. Two hours later she was running around outside in the sunshine, sharing a GF pizza from California Pizza Kitchen with me, and as happy as could be, and since then she seems to have total amnesia for the entire experience. Thankfully.

We received results 4 days later that her duodenal biopsies were normal and did not show celiac disease.  Since the biopsy results came back she has eaten gluten several times without getting ill or having digestive symptoms. I am glad that we went through with the testing. I’m not sure that this will last forever (just because she doesn’t have celiac disease now doesn’t mean that she won’t develop it in the future) and I have no idea why she was having the diarrhea or fevers, but for now I am grateful.

Out of curiosity, has anyone else had a toddler who seemed to have reactions to gluten that disappeared?

 

grade 1_2_2_2_5_2_2

Delay in Diagnosis of Celiac Disease

This is my first grade photo. This was taken right before I began to show signs and symptoms of Celiac Disease. Although it takes, on average, 10 to 13 years after the initial onset of symptoms for a patient with Celiac Disease to be diagnosed, in my case it took almost 30 years.

Undiagnosed, and hence, untreated, Celiac Disease is associated with anemia, osteoporosis, arthritis, infertility, central nervous system damage, and the development of other autoimmune diseases. Celiacs with longstanding exposure to gluten are also at an increased risk of cancer of the digestive system. Although some of these problems, such as anemia and infertility, are reversible once gluten free, others are not. My autoimmune thyroid disease (Hashimoto’s thyroiditis), which I suspect is due to decades of gluten exposure, will never go away.  Through the internet I have interacted with tons of other people with Celiac Disease with long delays in diagnosis (some not until their 50s or 60s). Anecdotally, it seems like a lot of us have multiple autoimmune issues, such as lupus, multiple sclerosis, fibromyalgia, and/or irritable bowel syndrome, as well as multiple food intolerances. It is unclear whether or not we would have developed these additional autoimmune problems had we removed gluten from our diets decades earlier, when we first started to show signs and symptoms of Celiac Disease. My gut tells me that we would have…

There was an interesting study published in Wales in 2007 in which the medical records of patients with Celiac Disease were reviewed. Celiac patients had a significant increase in number of subspecialist consultations in the years before diagnosis, seeing on average 5 different consultants. People with Celiac Disease also had symptoms of depression, anxiety, anemia, and diarrhea in much higher numbers than patients without Celiac Disease prior to diagnosis; 41% had a history of depression and/or anxiety. Swedish researchers examined the quality of life of 1500+ patients with Celiac Disease, both pre- and post-diagnosis, and found, not surprisingly, an improved quality of life for Celiac patients once diagnosed and treated (see link).

Last of all, a case report of a women diagnosed with Celiac Disease in her mid-forties (named Mrs. J) was published in a large medical journal called JAMA in 2011. Mrs. J’s main symptoms of Celiac Disease were recurrent miscarriages and chronic anemia. While I highly recommend that all of you read the article if you can, I am going to cut and paste a few of Mrs. J’s questions after diagnosis and the experts’ answers to her:

Could my miscarriages have been related to celiac disease? Currently the typical newly diagnosed patient with celiac disease is a woman around the age of 40 years who has had symptoms of celiac disease for over a decade. Given that active celiac disease has nutritional and direct inflammatory consequences on fertility, the reproductive life of many patients is irreversibly affected. In particular, the risk of miscarriage appears higher in women with untreated celiac disease compared to the general population. For these reasons, clinicians should maintain a very low threshold for celiac disease testing in this population.

Has my body sustained any irreversible damage from celiac disease over the years? The small intestinal mucosa has enormous regenerative capacity in both health and disease. Even individuals with longstanding, severe celiac enteropathy can expect to achieve complete or near complete intestinal healing with gluten avoidance and nutritional support, although the length of time to healing varies from less than one year to more than five years and healing is associated with younger age at diagnosis and improved GFD adherence. Outside of the intestine, however, healing is not always assured. A number of extraintestinal manifestations of celiac disease such as dermatitis herpetiformis, anemia, and joint pain, typically improve significantly or resolve within the first year of treatment, as was seen in Ms. J. One of the most common associations with celiac disease is reduced bone mineral density (BMD) which is seen in at more than 50% of patients at diagnosis. Although there is often a significant improvement in BMD over the first year of treatment with a GFD, up to 21% of patients will have persistent osteoporosis. There are multiple neurologic manifestations of celiac disease, some of including peripheral neuropathy and headaches which resolve, while case studies suggest that other manifestations including ataxia, may stabilize but rarely improve. Finally, there is a potential increased risk of secondary autoimmune disorders related to longstanding untreated celiac disease, and once triggered, these will not respond to gluten withdrawal.

My hope is that no child with current symptoms of Celiac Disease will have to wait 20+ years for diagnosis, like so many of us did. We need to prevent Celiac-associated problems, such as infertility, neurologic complications, and other autoimmune diseases, from developing in the first place, so that children with Celiac Disease can have an improved quality of life as adults!

References:

1. A case-control study of presentations in general practice before diagnosis of coeliac disease. Cannings-John R, Butler CC, Prout H, Owen D, Williams D, Hood K, Crimmins R, Swift G. Br J Gen Pract. 2007 Aug; 57(541):636-42.

2. Delay to celiac disease diagnosis and its implications for health-related quality of life. Norström F, Lindholm L, Sandström O, Nordyke K, Ivarsson A. BMC Gastroenterol. 2011 Nov 7;11:118.

3. Celiac disease diagnosis and management: a 46-year-old woman with anemia. Leffler D. Source Department of Gastroenterology, Beth Israel Deaconess Medical Center, and Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215, USA. dleffler@caregroup.harvard.edu. JAMA. 2011 Oct 12;306(14):1582-92.