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Celiac Disease and Lymphoma: Researcher Explains the Risk

August 14, 2013

Celiac Disease and Lymphoma: Researcher Explains the Risk


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Benjamin Lebwohl, MD, MS responds to questions about his recent study on the celiac disease and lymphoma association.

While the connection between celiac disease and its trigger (gluten) are well-understood, there are still many areas surrounding the autoimmune disease that cause uncertainty in the research world. For example, the medical literature is conflicting on the need for follow-up intestinal biopsies following the adoption of the gluten-free diet. Also unclear is the risk for developing lymphoma in people with celiac disease with either persistent villous atrophy or mucosal healing. Researchers examined this risk in a recent study published in Annals of Internal Medicine.

Researcher Benjamin Lebwohl, MD, MS, Assistant Professor of Medicine and Epidemiology at the Celiac Disease Center at Columbia University responded to the following questions to address the concerns of the celiac disease community.

Question 1

Q. One of the goals of this study is to determine the need for follow-up biopsies to confirm intestinal healing after people adopt the gluten-free diet. Why has this been unclear in the past? Did this study definitively determine the need for follow-up biopsies?

A. The reason for performing a follow-up biopsy has changed over time. Prior to the availability of high-quality blood tests for celiac disease, a follow-up biopsy was necessary to confirm the diagnosis. Now that we can follow blood tests to normalization while on the diet, the biopsy in usually not necessary for this purpose. Still, some patients will have persistent villous atrophy in the face of normalized blood tests and improved symptoms. The clinical significance of this finding is subject to debate. Our study shows that the results of the follow-up biopsy can risk-stratify patients regarding the risk of lymphoma. But I would not say that this study definitively determines the need for follow-up biopsy—rather, it provides an evidence-based rationale for that approach. Routinely performing follow-up biopsy is still a practice for which there’s legitimate debate.

Question 2

Q. Persistent villous atrophy is mainly caused by the continued consumption of gluten (intentionally or not). Are there other factors that can contribute to this lack of intestinal healing?

A. Persistent villous atrophy is certainly more common in patients who report poor adherence to the gluten-free diet, and so adherence is probably a major factor. But it’s not always the case that we can identify ongoing gluten exposure in patients with persistent villous atrophy. In some patients, persistent villous atrophy may be present after one year on the diet, but with more time healing occurs. So a one-time biopsy result is really just a snapshot. As for other factors that contribute to a lack of healing, this is not well understood at this time. It appears that older patients are slower to heal than younger patients, but this is still an area in need of investigation.

Question 3

Q. Prior to this study, what did researchers believe about the risk of lymphoma in people with celiac disease? Has this study proved or disproved their beliefs?

A. The link between celiac disease and lymphoma has been long known, and this study is consistent with prior findings that patients with celiac disease are at increased risk of developing lymphoma. What is new here is that the risk of lymphoma is not equally distributed among all patients with celiac disease. Rather, those who heal on follow-up biopsy have a significantly lower risk of lymphoma, approaching that of the general population, while those with persistent villous atrophy have an increased risk.

Question 4

Q. In comparison with the general population, how much higher is the risk of lymphoma for people with persistent villous atrophy? For those with intestinal healing?

A. Compared to the general population, patients with persistent villous atrophy had a 3.78-fold increase, while those with healing had only a 1.5-fold increase. These are relative increases, and it is important to bear in mind that, despite these differences in the healed vs. not-healed groups, the absolute risk of developing lymphoma in all of these groups is low. To put things in perspective based on the results of our study: over the next 10 years, the overall risk of lymphoma in a celiac disease patient is 7 in 1000. A patient with persistent villous atrophy has a 10 in 1000 risk, while a patient with healed intestines has a 4 in 1000 risk. So while there are differences here, the vast majority of celiac disease patients never develop lymphoma.

Question 5

Q. Which specific types of lymphoma do people with celiac disease have a higher risk of developing?

A. Non-Hodgkin lymphoma, which is an umbrella term for several types of lymphoma, both B cell and T cell derived. There is also a type of lymphoma called enteropathy associated T cell lymphoma, which has a poor prognosis and is closely associated with celiac disease in that it is rare in non-celiac patients. Fortunately, that type of lymphoma is quite rare.

Question 6

Q. In light of these findings, should people diagnosed with celiac disease have annual biopsies? Has this study produced a new recommendation for follow-up care?

A. This study provides an evidence-based rationale for performing a follow-up biopsy to confirm intestinal healing. But no guidelines mandate such a routine practice, and so this is left to the individual practitioner. My own practice is to consider one follow-up biopsy in the asymptomatic patient 2 years after starting the gluten-free diet. If healing has occurred, I do not do subsequent biopsies unless new symptoms or problems develop.

Question 7

Q. Is lymphoma associated with celiac disease more common in certain age groups or genders? How does the length of time without a diagnosis play into the risk? Does age of diagnosis (regardless of time of celiac disease onset) appear to increase or decrease the risk?

A. In our study lymphoma was more common in adults than children, which is similar to the general population. Age is the dominant risk factor. Length of time without a diagnosis has not been adequately studied—this is a difficult issue to study since (in the absence of stored blood) it is impossible to be certain how long an individual has had celiac disease.

Question 8

Q. Since the results suggest a higher risk of lymphoma, especially in those without mucosal healing, do you recommend people with celiac disease educate themselves on possible symptoms? How much of a concern are these results for the celiac disease community?

A. Lymphoma is not the kind of cancer that is typically screened for, unlike breast cancer and colon cancer, for example. The symptoms of lymphoma can be vast and might include persistently swollen or firm lymph nodes, weight loss, and night sweats. But it must be emphasized that the absolute risk of lymphoma in celiac disease patients is quite low, with the vast majority of individuals never developing this condition.

Question 9

Q. What do these study results suggest about the importance of adherence to a strict, lifelong gluten-free diet?

A. Since persistent villous atrophy is often a reflection of gluten exposure, this study supports the notion that strict adherence may decrease one’s risk of long-term complications.

Question 10

Q. Potential pharmaceutical treatments for celiac disease are currently in development. Would you say this study emphasizes the need for treatments in addition to or outside of the gluten-free diet?

A. Many patients are eager for non-dietary treatments to use in addition to (if not as a substitute for) a gluten-free diet, and the recent interest on the part of the research and pharmaceutical community is welcome.

Question 11

Q. Can we expect to see more research on the lymphoma and celiac disease connection in the future? Would you expect researchers to examine risks of other cancers as well?

A. While there has been a good deal of study examining the risk of various cancers in patients with celiac disease, my hope is that we will see more studies that emphasize risk modification and prevention. That is to say, now that we know about complications, can we effectively lower the risks and improve longevity and quality of life?


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