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Part 3: Celiac Disease Q&A with Dr. Stefano Guandalini, MD

Find answers to your celiac questions.

Stefano Guandalini, MD

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1. What are the most common comorbidities associated with celiac disease?

Since celiac disease is so common, the list can be quite long. It is important to distinguish which conditions occur more frequently in people with celiac disease and differentiate these by conditions that occur just as often in the general population. 

The best-known associations are autoimmune conditions like type 1 diabetes and thyroid disease. This is because celiac is an autoimmune disease that shares many common genes with other autoimmune conditions.

There are also chromosomal disorders such as Down syndrome, Turner syndrome and Williams syndrome that have a higher prevalence. Then there are many conditions that are neither autoimmune nor chromosomal that seem associated with celiac disease. This includes cardiovascular conditions, cerebrovascular diseases and musculoskeletal conditions, but making a comprehensive list would require more time and research.


2. And how concerned should people diagnosed with celiac disease be about these associated conditions? 

For example, when I refer to cardiovascular diseases like myocardial infarction, congestive heart failure and peripheral vascular disease, those occur 1.5 to 3 times more often in patients with celiac disease than in the general population. Liver and renal diseases are more frequent. Peptic ulcer disease is 3 to 4 times more frequent. The risk of lymphoma and leukemia appears to be more or less twice as common in patients with celiac disease. 

However, while the risk is more frequent, the total numbers remain relatively low. For example, let's say out of 15,000 individuals, the risk would increase from 500 to about 700 individuals affected. It's also important to note that the prevalence of some of these conditions can also decrease if the patient is on a stable and well-controlled gluten-free diet.  


3. Can you please explain the relationship between autoimmune arthritis, other autoimmune diseases and celiac disease? Why are they connected? 

Well, we currently only know part of the answer. New data seems to relate autoimmune conditions and celiac disease to a combination of genetic and environmental factors. 

The genetic factors are quite well known; they have to do with some associations with genes belonging to a class called HLA. As many of you probably know, celiac disease only occurs in individuals with HLA-DQ2 or DQ8. These genes are part of an assay (or group of genes), DR3 or DR4, which are also present in autoimmune conditions.

Among environmental factors, the most recent culprit appears to be viral infections. Viral infections caught during the first year of life, in particular, play a role in the onset of celiac disease and possibly type 1 diabetes, as well as some other autoimmune conditions. 

Additional factors that may increase the risk of celiac patients developing other autoimmune conditions include being female, having a family history of autoimmune disorders, being vitamin D deficient or testing positive for anti-gliadin IgG. 

4. How do you differentiate between the gradual physical changes of aging from possible celiac disease comorbidities? 

One of the first things you can do if you think there is a problem is to take tests like the ones imaware produces to assess your heart, thyroid, etc. Then you can discuss your results with your healthcare provider. A lot of this comes back to whether you have a healthcare provider you trust and who is familiar enough with celiac disease to investigate whether your problems are associated with celiac.

Another thing to consider is celiac serology. If the serology remains normal, though it is not a 100% correlation, this will indicate that what's occurring is probably unrelated to celiac.  

 5. Can the inflammation caused by celiac disease set someone up for more significant cardiac disease risks? 

In the study we did a few years ago, we found a much higher prevalence of cardiovascular disease in patients with celiac disease. While we don't know the exact factors, the systemic inflammation that is part of celiac disease likely contributes to this problem. This is where tests like the hs-CRP test can be helpful in the earlier detection of inflammation that goes beyond what is expected of celiac disease.


6. Can a gluten-free diet help those with autoimmune diseases other than celiac disease?  

Studies are trying to address this, but the evidence is relatively weak. In other words, we don't have enough evidence to suggest that a gluten-free diet will help improve the clinical status of patients with rheumatoid arthritis, Sjogren's, psoriasis or type 1 diabetes. Lack of evidence does not mean it's impossible, but there is no current evidence that the gluten-free diet helps in other autoimmune conditions besides celiac disease (and some sensitivities, but that's another conversation). I do not recommend that anyone starts a gluten-free diet unless they are medically required to.

7. Do you think individuals with type 1 diabetes should be tested for celiac disease and vice versa? 

Most definitely. If you are diagnosed with type 1 diabetes, you should be tested for celiac disease and vice versa. All the significant gastrointestinal and endocrinological societies that are involved in providing guidelines for patients diagnosed or suspected to be diagnosed with type 1 diabetes do recommend testing for celiac disease at the time of diagnosis. The prevalence of unknown celiac disease at the time of diagnosis of diabetes is around 10%, making it about ten times more common than in the general population. 

There are two other things I want to note. First, it is common for type 1 diabetics diagnosed with celiac disease to have experienced little or no symptoms, so everyone with diabetes should be tested regardless of symptoms or not. The second thing I want to mention is that, unfortunately, if you test negative for celiac disease at the time of your type 1 diabetes diagnosis, you can still develop celiac disease later on. How often you should be retested depends on the individual, but it is generally recommended at least every couple of years. 

8. Can you explain the relationship between celiac disease, anxiety, depression and mental health?

I wish I could, but I don't think anyone knows the exact connection. Unfortunately, the prevalence of anxiety and depression in patients with celiac disease is higher. A study reported that celiac patients on gluten-free diets appeared to have a higher prevalence when compared with celiac patients who refuse to follow the diet, which is interesting and a bit counterintuitive. One of the reasons could be that they feel the social burden of being gluten-free. You can imagine the isolation of being different, of not being able to enjoy pizza with friends, etc. It can be a pretty demanding condition, so that might contribute.

Another thing that might have something to do with it is the microbiota. There is a gut-microbiota-brain axis that has been well explored in recent years, and one of the positive effects of healthy microbiota is that it helps maintain a steady mood by relieving stress and anxiety. So vice versa might also be correct, though this is just speculation.  

Back to the root of the question: Can I explain why this association exists? I think we don’t have all the elements we need to answer that. 


9. Is there a connection between colitis and celiac disease?

Yes, there is, but first, let's define colitis because it can mean many different things. 

Ulcerative colitis is part of inflammatory bowel disease and is a condition that has an autoimmune component. So yes, although not very high, there is an increased risk of association between ulcerative colitis and celiac disease.

It's different for microscopic colitis, which is a diagnosis in which the colonoscopy will not disclose any ulcers, but there is microscopic inflammation that leads to watery diarrhea and other symptoms. Lymphocytic colitis, also part of microscopic colitis, is strongly associated with celiac disease. It does tend to respond initially to a gluten-free diet, but in most cases, you also need to add a specific treatment for colitis, such as a steroid or other available preparations.

10. Celiac disease and irritable bowel syndrome (IBS) can be very similar, is there a way to differentiate them?  

IBS and untreated celiac disease do have many of the same symptoms, like diarrhea, abdominal pain and bloating. However, untreated celiac disease is also associated with nutritional deficiencies, which may manifest as weight loss or the inability to gain weight. This is one way to differentiate between them. Then, of course, there are tests. Though there is no specific test for IBS, there is one for celiac disease that can be very helpful. 


11. None of my family members had celiac disease before my daughter was diagnosed. How does this exist without a family history?   

First of all, I would challenge the absence of family history. Celiac disease is very prevalent, so you may have had relatives with celiac who went through life undiagnosed because they had minimal symptoms. The fact that there is no known celiac patient doesn't rule out the possible presence of celiac disease. 

That said, many new patients are diagnosed with no family history of celiac disease — it happens all the time. 


12. What percentage of people with celiac disease on a strict gluten-free diet develop stomach or intestinal cancers? 

It seems that if you are diagnosed with celiac disease and are on a gluten-free diet, the crucial period is the first two to three years; in other words, if you do not develop cancer associated with celiac during the first couple of years after the diagnosis and stick to a gluten-free diet, then your prevalence is the same risk as the general population. However, patients who do not follow the diet are a different story.


13. Is there a connection between celiac disease and lactose intolerance?

Yes, there is a connection. Celiac disease affects the small intestine causing the villi — tiny finger-like projections inside the small intestine — to become blunted. Lactase, the enzyme that enables us to digest lactose, is anchored on the top of the villi, so when you lose the villi, you lose the lactase. Therefore, no lactase leads to symptoms like bloating, diarrhea and abdominal pain when you consume lactose. 

A gluten-free diet can hopefully normalize the villi, though this does not always happen. In kids, it takes no more than three to four weeks to get back to normal lactase though adults might take a bit longer. Therefore, eliminating lactose is only recommended if you have symptoms and only for the first couple of months on the gluten-free diet. 


14. Are you optimistic that there will be additional treatments for celiac disease in the future?  

I am optimistic because I know many, if not most, players involved in this active research. I know how engaged they are and how rigorous their methodologies are. In addition, I've been able to act as a reviewer of papers submitted for publication with advancement done in different areas of research, from a pill that would limit the intestinal permeability to gluten to medicines that would degrade gluten in your stomach to other processes that would prevent the trigger of the immune response to gluten. The three areas I have briefly mentioned yield significant preliminary and even not-so-much preliminary results, so there are good reasons for being optimistic. 

Missed the first two Q&As? Check out Part 1 and Part 2 now.

Updated on
January 30, 2023
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