2015 Advances In IBD

HOLLYWOOD, FLA. – Current and previous use of thiopurines, biologics, and combination therapies are all independent risk factors for skin cancer, according to expert analysis given at a conference on inflammatory bowel diseases.

Although population-based cohort studies have shown that the baseline risk for nonmelanoma skin cancer in IBD has risen more than a third since the preimmunomodulator era, regardless of the mode of treatment, "Cutaneous side effects of immunomodulators and biologics are a rising concern in clinical practice," said Dr. Jean-Frederic Colombel of the Icahn School of Medicine at Mount Sinai in New York. "Patients with Crohn’s disease in particular have shown a twofold increased risk for nonmelanoma skin cancer, outside of any kind of immunomodulator or biologic therapy."

Thiopurine use has been associated with a twofold increased risk of nonmelanoma skin cancer that persists even after withdrawal from the medication, although there is not an increased risk for melanoma, according to Dr. Colombel.

In a comparative analysis of studies published primarily since 2011, he noted an epidemiologic study with an A level of evidence for nearly 10,000 IBD patients undergoing thiopurine treatment that had an increased risk for NMSC with an odds ratio of approximately 2.2 (95% CI, 1.24-3.81).

"What is very important to note is that the risk of nonmelanoma skin cancer persists even after the antimetabolite has been stopped," said Dr. Colombel, referring to data from the CESAME study that indicated, regardless of age, past and current thiopurine use was associated with higher incidence rates of NMSC.

To date, other immunomodulators have not been associated with NMSC, said Dr. Colombel. "What we are observing is quite specific to azathioprine."

Thiopurines are not considered a risk factor for melanoma, said Dr. Colombel. He cited a study of records from a health care claims database for the period between 1997 and 2009. In the study, 209 melanoma cases were matched with 823 controls. Exposure to thiopurines was associated with an OR of 1.1 for melanoma. In that same study, patients exposed to biologics were found to have an increased risk of melanoma, although the risk was higher in patients with Crohn’s disease than those with ulcerative colitis (OR, 1.94 vs. 1.73).

Biologics may also increase the risk of NMSC, although currently the data are "controversial" said Dr. Colombel. "The results are more difficult to interpret."

The risk for NMSC in IBD patients exposed to biologics was evaluated in three studies published between 2010 and 2013. One study indicated no significant increased risk for either past or current biologic use (OR 1.14, 95% CI 0.95-1.36).

Another study indicated a twofold increased risk for patients who’d withdrawn from biologic therapy (OR 2.07, 95% CI 1.28-3.33) and who had persistent use (OR 2.18, 95% CI, 1.07-4.46).

A third study showed a 2.3 increased NMSC risk (95% CI, 1.44-3.47).

In a meta-analysis published in 2013, the pooled relative risk for melanoma in IBD patients exposed to biologics was not shown to be significant (RR, 1.10).

Combination therapy has been found to increase the risk of NMSC nearly fourfold, said Dr. Colombel.

Even though more data are needed, Dr. Colombel said that all patients who are scheduled to start immunosuppression should be informed of the potential for dermatologic complications. "Personally, I am now sending all my patients to a dermatologist for a baseline evaluation," he said.

The conference was sponsored by the Crohn’s & Colitis Foundation of America. Dr. Colombel reported many disclosures, including Abbott Laboratories, Bristol-Myers Squibb, Genentech, Inc., Pfizer Inc. and sanofi-aventis, among others.

wmcknight@frontlinemedcom.com

HOLLYWOOD, FLA. – Current and previous use of thiopurines, biologics, and combination therapies are all independent risk factors for skin cancer, according to expert analysis given at a conference on inflammatory bowel diseases.

Although population-based cohort studies have shown that the baseline risk for nonmelanoma skin cancer in IBD has risen more than a third since the preimmunomodulator era, regardless of the mode of treatment, "Cutaneous side effects of immunomodulators and biologics are a rising concern in clinical practice," said Dr. Jean-Frederic Colombel of the Icahn School of Medicine at Mount Sinai in New York. "Patients with Crohn’s disease in particular have shown a twofold increased risk for nonmelanoma skin cancer, outside of any kind of immunomodulator or biologic therapy."

Thiopurine use has been associated with a twofold increased risk of nonmelanoma skin cancer that persists even after withdrawal from the medication, although there is not an increased risk for melanoma, according to Dr. Colombel.

In a comparative analysis of studies published primarily since 2011, he noted an epidemiologic study with an A level of evidence for nearly 10,000 IBD patients undergoing thiopurine treatment that had an increased risk for NMSC with an odds ratio of approximately 2.2 (95% CI, 1.24-3.81).

"What is very important to note is that the risk of nonmelanoma skin cancer persists even after the antimetabolite has been stopped," said Dr. Colombel, referring to data from the CESAME study that indicated, regardless of age, past and current thiopurine use was associated with higher incidence rates of NMSC.

To date, other immunomodulators have not been associated with NMSC, said Dr. Colombel. "What we are observing is quite specific to azathioprine."

Thiopurines are not considered a risk factor for melanoma, said Dr. Colombel. He cited a study of records from a health care claims database for the period between 1997 and 2009. In the study, 209 melanoma cases were matched with 823 controls. Exposure to thiopurines was associated with an OR of 1.1 for melanoma. In that same study, patients exposed to biologics were found to have an increased risk of melanoma, although the risk was higher in patients with Crohn’s disease than those with ulcerative colitis (OR, 1.94 vs. 1.73).

Biologics may also increase the risk of NMSC, although currently the data are "controversial" said Dr. Colombel. "The results are more difficult to interpret."

The risk for NMSC in IBD patients exposed to biologics was evaluated in three studies published between 2010 and 2013. One study indicated no significant increased risk for either past or current biologic use (OR 1.14, 95% CI 0.95-1.36).

Another study indicated a twofold increased risk for patients who’d withdrawn from biologic therapy (OR 2.07, 95% CI 1.28-3.33) and who had persistent use (OR 2.18, 95% CI, 1.07-4.46).

A third study showed a 2.3 increased NMSC risk (95% CI, 1.44-3.47).

In a meta-analysis published in 2013, the pooled relative risk for melanoma in IBD patients exposed to biologics was not shown to be significant (RR, 1.10).

Combination therapy has been found to increase the risk of NMSC nearly fourfold, said Dr. Colombel.

Even though more data are needed, Dr. Colombel said that all patients who are scheduled to start immunosuppression should be informed of the potential for dermatologic complications. "Personally, I am now sending all my patients to a dermatologist for a baseline evaluation," he said.

The conference was sponsored by the Crohn’s & Colitis Foundation of America. Dr. Colombel reported many disclosures, including Abbott Laboratories, Bristol-Myers Squibb, Genentech, Inc., Pfizer Inc. and sanofi-aventis, among others.

wmcknight@frontlinemedcom.com

HOLLYWOOD, FLA. – Current and previous use of thiopurines, biologics, and combination therapies are all independent risk factors for skin cancer, according to expert analysis given at a conference on inflammatory bowel diseases.

Although population-based cohort studies have shown that the baseline risk for nonmelanoma skin cancer in IBD has risen more than a third since the preimmunomodulator era, regardless of the mode of treatment, "Cutaneous side effects of immunomodulators and biologics are a rising concern in clinical practice," said Dr. Jean-Frederic Colombel of the Icahn School of Medicine at Mount Sinai in New York. "Patients with Crohn’s disease in particular have shown a twofold increased risk for nonmelanoma skin cancer, outside of any kind of immunomodulator or biologic therapy."

Thiopurine use has been associated with a twofold increased risk of nonmelanoma skin cancer that persists even after withdrawal from the medication, although there is not an increased risk for melanoma, according to Dr. Colombel.

In a comparative analysis of studies published primarily since 2011, he noted an epidemiologic study with an A level of evidence for nearly 10,000 IBD patients undergoing thiopurine treatment that had an increased risk for NMSC with an odds ratio of approximately 2.2 (95% CI, 1.24-3.81).

"What is very important to note is that the risk of nonmelanoma skin cancer persists even after the antimetabolite has been stopped," said Dr. Colombel, referring to data from the CESAME study that indicated, regardless of age, past and current thiopurine use was associated with higher incidence rates of NMSC.

To date, other immunomodulators have not been associated with NMSC, said Dr. Colombel. "What we are observing is quite specific to azathioprine."

Thiopurines are not considered a risk factor for melanoma, said Dr. Colombel. He cited a study of records from a health care claims database for the period between 1997 and 2009. In the study, 209 melanoma cases were matched with 823 controls. Exposure to thiopurines was associated with an OR of 1.1 for melanoma. In that same study, patients exposed to biologics were found to have an increased risk of melanoma, although the risk was higher in patients with Crohn’s disease than those with ulcerative colitis (OR, 1.94 vs. 1.73).

Biologics may also increase the risk of NMSC, although currently the data are "controversial" said Dr. Colombel. "The results are more difficult to interpret."

The risk for NMSC in IBD patients exposed to biologics was evaluated in three studies published between 2010 and 2013. One study indicated no significant increased risk for either past or current biologic use (OR 1.14, 95% CI 0.95-1.36).

Another study indicated a twofold increased risk for patients who’d withdrawn from biologic therapy (OR 2.07, 95% CI 1.28-3.33) and who had persistent use (OR 2.18, 95% CI, 1.07-4.46).

A third study showed a 2.3 increased NMSC risk (95% CI, 1.44-3.47).

In a meta-analysis published in 2013, the pooled relative risk for melanoma in IBD patients exposed to biologics was not shown to be significant (RR, 1.10).

Combination therapy has been found to increase the risk of NMSC nearly fourfold, said Dr. Colombel.

Even though more data are needed, Dr. Colombel said that all patients who are scheduled to start immunosuppression should be informed of the potential for dermatologic complications. "Personally, I am now sending all my patients to a dermatologist for a baseline evaluation," he said.

The conference was sponsored by the Crohn’s & Colitis Foundation of America. Dr. Colombel reported many disclosures, including Abbott Laboratories, Bristol-Myers Squibb, Genentech, Inc., Pfizer Inc. and sanofi-aventis, among others.

wmcknight@frontlinemedcom.com

HOLLYWOOD, FLA. – Refractory celiac disease is often the result of patients having either received an incorrect diagnosis, or their noncompliance, according to Dr. Joseph Murray of the Mayo Clinic in Rochester, Minn.

"When faced with such a patient, it’s important to reconfirm the original diagnosis," said Dr. Murray, who made his remarks during a clinical track presentation at a conference on inflammatory bowel.

In cases in which the diagnosis can be confirmed and the patient is compliant, discovering if there are other conditions, and whether to intervene and how, are the important next steps, according to Dr. Murray.

When patients present with symptoms of nonresponsive celiac disease, besides taking the patient’s history, which should include whether the patient has any first-degree family members with "true" celiac disease, not just family members who have chosen to stop eating gluten, "I will always ask for the original biopsies," said Dr. Murray.

In addition, original serology tests, if they were done, can confirm whether there are celiac-specific antibodies. "Gliadin antibodies are not celiac specific," said Dr. Murray. "You can get gliadin antibodies in virtually every other disorder that affects the intestines, so they are pretty much worthless." Better specificity comes from tissue transglutaminase or endomysial antibodies, he said at the meeting diseases sponsored by the Crohn’s & Colitis Foundation of America.

Human leukocyte antigen genotyping, and whether the patient had a clinically obvious response to a gluten-free diet also will help the clinician puzzle out if the original diagnosis was correct, according to Dr. Murray. Worth noting is whether the patient has dermatitis herpetiformis, "That’s pathognomonic for celiac disease," said Dr. Murray.

For example, in the case of a 90-year-old woman whose biopsy 10 years before had been interpreted as presumptive celiac disease and who had had an initial response to a gluten-free diet, had symptoms that persisted for a decade because she’d contracted tropical sprue from annual visits to Indonesia that were not noted in her original patient history. Treated properly, her symptoms abated entirely, according to Dr. Murray. "She wasn’t exactly happy about her 10 years of living gluten free," he said.

Dangers of noncompliance

As for patients who claim to follow a gluten-free diet, "That’s not true most of the time," said Dr. Murray. "A positive serology test in a patient who’s been following a gluten-free diet for a year or more means they’re not just getting a little gluten. They’re getting a lot of gluten." It can either be advertent or inadvertently, he said.

However, serology is insensitive for lower levels of gluten contamination, but a gram of gluten, roughly one-half a slice of bread per day, can be detected, according to Dr. Murray.

If noncompliance is the reason for the refractory condition, patients are at greater risk for increased mortality, osteoporosis, lymphomas, and other cancers, and psychological effects such as depression. "Eliminating the gluten may take time. Often we have to use behavioral counselors to help," said Dr. Murray.

Also key is to stay in touch with the patient. "Follow-up in patients with celiac disease is abysmal," Dr. Murray said, "It’s almost like once the disease is diagnosed, it’s forgotten about medically."

"The complicating thing about celiac disease can be that autoimmune disorders and like disorders hang out together," said Dr. Murray. "Complications of celiac disease also can occur in multiples."

Bacterial overgrowth, microscopic colitis, lymphoma, and systemic sclerosis associated–dysmotility are all concurrent conditions Dr. Murray reported seeing in his own practice when treating refractory celiac disease.

Because lactose intolerance is also common in celiac disease, Dr. Murray said he will often advises patients to avoid dairy for a year, and then gradually add that back into the diet with good results. "Often, that will work, so I don’t even test for lactose intolerance initially," he said.

Despite all the possible etiologies for nonresponsive celiac disease, gluten exposure was found in more than a third of cases, while "true refractory celiac disease really makes up only about 10% or 11% of these nonresponsive patients," said Dr. Murray, referring to a study on the topic (Clin. Gastroenterol. Hepatol. 2007;5:445-50).

Patients with celiac disease also can have multifocal strictures in the proximal duodenum that reach the jejunum, "but rarely affect the ileum," according to Dr. Murray.

Possible lymphomas

"The first thing that I think about when I see a really sick patient previously diagnosed with celiac disease several years before is, ‘Does the patient have lymphoma?’" said Dr. Murray. Ulcerative jejunoileitis typically indicates that lymphoma is imminent, although shallower ulcers are often linked to the use of NSAIDs, he said.

Giant cavitating lymphadenopathy, while rare, is also a consideration, according to Dr. Murray. "A premalignant type of disorder, sometimes will respond to immunosuppressives, but often can presage the development of lymphoma," he said.

True refractory celiac disease involves symptomatic malabsorption, severe enteropathy, and a primary or secondary nonresponse to a gluten-free diet. "By definition, there should be no lymphoma," said Dr. Murray.

Refractory celiac disease is either characterized as type 1, which has a normal T-cell population and responds well to immunosuppression, or as type 2 with clonal T cells.

Dr. Murray said he often uses topical budesonide to treat type 1 patients, with good results, since there is about a 90% recovery rate in this patient population. Type 2 is the most pernicious, with nearly half of patients dying within 5 years of diagnosis, either from malignant or infectious complications, according to Dr. Murray. "Type 2 refractory disease is not a trivial disease," he said.

Although most adults with celiac disease don’t heal, many are asymptomatic; however, this does not mean a patient’s risk of mortality from the disease has improved. Patients are also at greater risk for malignant complications. (Am. J. Gastroenterol. 2010;105:1412-20 [doi:10.1038/ajg.2010.10]).

"We really don’t know what we should do about those asymptomatic patients," said Dr. Murray. He noted that, "Failure to heal is not entirely benign, but it’s not refractory celiac disease," said Dr. Murray.

Dr. Murray stated that he had no disclosures.

wmcknight@frontlinemedcom.com

HOLLYWOOD, FLA. – Refractory celiac disease is often the result of patients having either received an incorrect diagnosis, or their noncompliance, according to Dr. Joseph Murray of the Mayo Clinic in Rochester, Minn.

"When faced with such a patient, it’s important to reconfirm the original diagnosis," said Dr. Murray, who made his remarks during a clinical track presentation at a conference on inflammatory bowel.

In cases in which the diagnosis can be confirmed and the patient is compliant, discovering if there are other conditions, and whether to intervene and how, are the important next steps, according to Dr. Murray.

When patients present with symptoms of nonresponsive celiac disease, besides taking the patient’s history, which should include whether the patient has any first-degree family members with "true" celiac disease, not just family members who have chosen to stop eating gluten, "I will always ask for the original biopsies," said Dr. Murray.

In addition, original serology tests, if they were done, can confirm whether there are celiac-specific antibodies. "Gliadin antibodies are not celiac specific," said Dr. Murray. "You can get gliadin antibodies in virtually every other disorder that affects the intestines, so they are pretty much worthless." Better specificity comes from tissue transglutaminase or endomysial antibodies, he said at the meeting diseases sponsored by the Crohn’s & Colitis Foundation of America.

Human leukocyte antigen genotyping, and whether the patient had a clinically obvious response to a gluten-free diet also will help the clinician puzzle out if the original diagnosis was correct, according to Dr. Murray. Worth noting is whether the patient has dermatitis herpetiformis, "That’s pathognomonic for celiac disease," said Dr. Murray.

For example, in the case of a 90-year-old woman whose biopsy 10 years before had been interpreted as presumptive celiac disease and who had had an initial response to a gluten-free diet, had symptoms that persisted for a decade because she’d contracted tropical sprue from annual visits to Indonesia that were not noted in her original patient history. Treated properly, her symptoms abated entirely, according to Dr. Murray. "She wasn’t exactly happy about her 10 years of living gluten free," he said.

Dangers of noncompliance

As for patients who claim to follow a gluten-free diet, "That’s not true most of the time," said Dr. Murray. "A positive serology test in a patient who’s been following a gluten-free diet for a year or more means they’re not just getting a little gluten. They’re getting a lot of gluten." It can either be advertent or inadvertently, he said.

However, serology is insensitive for lower levels of gluten contamination, but a gram of gluten, roughly one-half a slice of bread per day, can be detected, according to Dr. Murray.

If noncompliance is the reason for the refractory condition, patients are at greater risk for increased mortality, osteoporosis, lymphomas, and other cancers, and psychological effects such as depression. "Eliminating the gluten may take time. Often we have to use behavioral counselors to help," said Dr. Murray.

Also key is to stay in touch with the patient. "Follow-up in patients with celiac disease is abysmal," Dr. Murray said, "It’s almost like once the disease is diagnosed, it’s forgotten about medically."

"The complicating thing about celiac disease can be that autoimmune disorders and like disorders hang out together," said Dr. Murray. "Complications of celiac disease also can occur in multiples."

Bacterial overgrowth, microscopic colitis, lymphoma, and systemic sclerosis associated–dysmotility are all concurrent conditions Dr. Murray reported seeing in his own practice when treating refractory celiac disease.

Because lactose intolerance is also common in celiac disease, Dr. Murray said he will often advises patients to avoid dairy for a year, and then gradually add that back into the diet with good results. "Often, that will work, so I don’t even test for lactose intolerance initially," he said.

Despite all the possible etiologies for nonresponsive celiac disease, gluten exposure was found in more than a third of cases, while "true refractory celiac disease really makes up only about 10% or 11% of these nonresponsive patients," said Dr. Murray, referring to a study on the topic (Clin. Gastroenterol. Hepatol. 2007;5:445-50).

Patients with celiac disease also can have multifocal strictures in the proximal duodenum that reach the jejunum, "but rarely affect the ileum," according to Dr. Murray.

Possible lymphomas

"The first thing that I think about when I see a really sick patient previously diagnosed with celiac disease several years before is, ‘Does the patient have lymphoma?’" said Dr. Murray. Ulcerative jejunoileitis typically indicates that lymphoma is imminent, although shallower ulcers are often linked to the use of NSAIDs, he said.

Giant cavitating lymphadenopathy, while rare, is also a consideration, according to Dr. Murray. "A premalignant type of disorder, sometimes will respond to immunosuppressives, but often can presage the development of lymphoma," he said.

True refractory celiac disease involves symptomatic malabsorption, severe enteropathy, and a primary or secondary nonresponse to a gluten-free diet. "By definition, there should be no lymphoma," said Dr. Murray.

Refractory celiac disease is either characterized as type 1, which has a normal T-cell population and responds well to immunosuppression, or as type 2 with clonal T cells.

Dr. Murray said he often uses topical budesonide to treat type 1 patients, with good results, since there is about a 90% recovery rate in this patient population. Type 2 is the most pernicious, with nearly half of patients dying within 5 years of diagnosis, either from malignant or infectious complications, according to Dr. Murray. "Type 2 refractory disease is not a trivial disease," he said.

Although most adults with celiac disease don’t heal, many are asymptomatic; however, this does not mean a patient’s risk of mortality from the disease has improved. Patients are also at greater risk for malignant complications. (Am. J. Gastroenterol. 2010;105:1412-20 [doi:10.1038/ajg.2010.10]).

"We really don’t know what we should do about those asymptomatic patients," said Dr. Murray. He noted that, "Failure to heal is not entirely benign, but it’s not refractory celiac disease," said Dr. Murray.

Dr. Murray stated that he had no disclosures.

wmcknight@frontlinemedcom.com

HOLLYWOOD, FLA. – Refractory celiac disease is often the result of patients having either received an incorrect diagnosis, or their noncompliance, according to Dr. Joseph Murray of the Mayo Clinic in Rochester, Minn.

"When faced with such a patient, it’s important to reconfirm the original diagnosis," said Dr. Murray, who made his remarks during a clinical track presentation at a conference on inflammatory bowel.

In cases in which the diagnosis can be confirmed and the patient is compliant, discovering if there are other conditions, and whether to intervene and how, are the important next steps, according to Dr. Murray.

When patients present with symptoms of nonresponsive celiac disease, besides taking the patient’s history, which should include whether the patient has any first-degree family members with "true" celiac disease, not just family members who have chosen to stop eating gluten, "I will always ask for the original biopsies," said Dr. Murray.

In addition, original serology tests, if they were done, can confirm whether there are celiac-specific antibodies. "Gliadin antibodies are not celiac specific," said Dr. Murray. "You can get gliadin antibodies in virtually every other disorder that affects the intestines, so they are pretty much worthless." Better specificity comes from tissue transglutaminase or endomysial antibodies, he said at the meeting diseases sponsored by the Crohn’s & Colitis Foundation of America.

Human leukocyte antigen genotyping, and whether the patient had a clinically obvious response to a gluten-free diet also will help the clinician puzzle out if the original diagnosis was correct, according to Dr. Murray. Worth noting is whether the patient has dermatitis herpetiformis, "That’s pathognomonic for celiac disease," said Dr. Murray.

For example, in the case of a 90-year-old woman whose biopsy 10 years before had been interpreted as presumptive celiac disease and who had had an initial response to a gluten-free diet, had symptoms that persisted for a decade because she’d contracted tropical sprue from annual visits to Indonesia that were not noted in her original patient history. Treated properly, her symptoms abated entirely, according to Dr. Murray. "She wasn’t exactly happy about her 10 years of living gluten free," he said.

Dangers of noncompliance

As for patients who claim to follow a gluten-free diet, "That’s not true most of the time," said Dr. Murray. "A positive serology test in a patient who’s been following a gluten-free diet for a year or more means they’re not just getting a little gluten. They’re getting a lot of gluten." It can either be advertent or inadvertently, he said.

However, serology is insensitive for lower levels of gluten contamination, but a gram of gluten, roughly one-half a slice of bread per day, can be detected, according to Dr. Murray.

If noncompliance is the reason for the refractory condition, patients are at greater risk for increased mortality, osteoporosis, lymphomas, and other cancers, and psychological effects such as depression. "Eliminating the gluten may take time. Often we have to use behavioral counselors to help," said Dr. Murray.

Also key is to stay in touch with the patient. "Follow-up in patients with celiac disease is abysmal," Dr. Murray said, "It’s almost like once the disease is diagnosed, it’s forgotten about medically."

"The complicating thing about celiac disease can be that autoimmune disorders and like disorders hang out together," said Dr. Murray. "Complications of celiac disease also can occur in multiples."

Bacterial overgrowth, microscopic colitis, lymphoma, and systemic sclerosis associated–dysmotility are all concurrent conditions Dr. Murray reported seeing in his own practice when treating refractory celiac disease.

Because lactose intolerance is also common in celiac disease, Dr. Murray said he will often advises patients to avoid dairy for a year, and then gradually add that back into the diet with good results. "Often, that will work, so I don’t even test for lactose intolerance initially," he said.

Despite all the possible etiologies for nonresponsive celiac disease, gluten exposure was found in more than a third of cases, while "true refractory celiac disease really makes up only about 10% or 11% of these nonresponsive patients," said Dr. Murray, referring to a study on the topic (Clin. Gastroenterol. Hepatol. 2007;5:445-50).

Patients with celiac disease also can have multifocal strictures in the proximal duodenum that reach the jejunum, "but rarely affect the ileum," according to Dr. Murray.

Possible lymphomas

"The first thing that I think about when I see a really sick patient previously diagnosed with celiac disease several years before is, ‘Does the patient have lymphoma?’" said Dr. Murray. Ulcerative jejunoileitis typically indicates that lymphoma is imminent, although shallower ulcers are often linked to the use of NSAIDs, he said.

Giant cavitating lymphadenopathy, while rare, is also a consideration, according to Dr. Murray. "A premalignant type of disorder, sometimes will respond to immunosuppressives, but often can presage the development of lymphoma," he said.

True refractory celiac disease involves symptomatic malabsorption, severe enteropathy, and a primary or secondary nonresponse to a gluten-free diet. "By definition, there should be no lymphoma," said Dr. Murray.

Refractory celiac disease is either characterized as type 1, which has a normal T-cell population and responds well to immunosuppression, or as type 2 with clonal T cells.

Dr. Murray said he often uses topical budesonide to treat type 1 patients, with good results, since there is about a 90% recovery rate in this patient population. Type 2 is the most pernicious, with nearly half of patients dying within 5 years of diagnosis, either from malignant or infectious complications, according to Dr. Murray. "Type 2 refractory disease is not a trivial disease," he said.

Although most adults with celiac disease don’t heal, many are asymptomatic; however, this does not mean a patient’s risk of mortality from the disease has improved. Patients are also at greater risk for malignant complications. (Am. J. Gastroenterol. 2010;105:1412-20 [doi:10.1038/ajg.2010.10]).

"We really don’t know what we should do about those asymptomatic patients," said Dr. Murray. He noted that, "Failure to heal is not entirely benign, but it’s not refractory celiac disease," said Dr. Murray.

Dr. Murray stated that he had no disclosures.

wmcknight@frontlinemedcom.com

HOLLYWOOD, FLA. – Refractory celiac disease is often the result of patients having either received an incorrect diagnosis, or their noncompliance, according to Dr. Joseph Murray of the Mayo Clinic in Rochester, Minn.

"When faced with such a patient, it’s important to reconfirm the original diagnosis," said Dr. Murray, who made his remarks during a clinical track presentation at a conference on inflammatory bowel.

In cases in which the diagnosis can be confirmed and the patient is compliant, discovering if there are other conditions, and whether to intervene and how, are the important next steps, according to Dr. Murray.

When patients present with symptoms of nonresponsive celiac disease, besides taking the patient’s history, which should include whether the patient has any first-degree family members with "true" celiac disease, not just family members who have chosen to stop eating gluten, "I will always ask for the original biopsies," said Dr. Murray.

In addition, original serology tests, if they were done, can confirm whether there are celiac-specific antibodies. "Gliadin antibodies are not celiac specific," said Dr. Murray. "You can get gliadin antibodies in virtually every other disorder that affects the intestines, so they are pretty much worthless." Better specificity comes from tissue transglutaminase or endomysial antibodies, he said at the meeting diseases sponsored by the Crohn’s & Colitis Foundation of America.

Human leukocyte antigen genotyping, and whether the patient had a clinically obvious response to a gluten-free diet also will help the clinician puzzle out if the original diagnosis was correct, according to Dr. Murray. Worth noting is whether the patient has dermatitis herpetiformis, "That’s pathognomonic for celiac disease," said Dr. Murray.

For example, in the case of a 90-year-old woman whose biopsy 10 years before had been interpreted as presumptive celiac disease and who had had an initial response to a gluten-free diet, had symptoms that persisted for a decade because she’d contracted tropical sprue from annual visits to Indonesia that were not noted in her original patient history. Treated properly, her symptoms abated entirely, according to Dr. Murray. "She wasn’t exactly happy about her 10 years of living gluten free," he said.

Dangers of noncompliance

As for patients who claim to follow a gluten-free diet, "That’s not true most of the time," said Dr. Murray. "A positive serology test in a patient who’s been following a gluten-free diet for a year or more means they’re not just getting a little gluten. They’re getting a lot of gluten." It can either be advertent or inadvertently, he said.

However, serology is insensitive for lower levels of gluten contamination, but a gram of gluten, roughly one-half a slice of bread per day, can be detected, according to Dr. Murray.

If noncompliance is the reason for the refractory condition, patients are at greater risk for increased mortality, osteoporosis, lymphomas, and other cancers, and psychological effects such as depression. "Eliminating the gluten may take time. Often we have to use behavioral counselors to help," said Dr. Murray.

Also key is to stay in touch with the patient. "Follow-up in patients with celiac disease is abysmal," Dr. Murray said, "It’s almost like once the disease is diagnosed, it’s forgotten about medically."

"The complicating thing about celiac disease can be that autoimmune disorders and like disorders hang out together," said Dr. Murray. "Complications of celiac disease also can occur in multiples."

Bacterial overgrowth, microscopic colitis, lymphoma, and systemic sclerosis associated–dysmotility are all concurrent conditions Dr. Murray reported seeing in his own practice when treating refractory celiac disease.

Because lactose intolerance is also common in celiac disease, Dr. Murray said he will often advises patients to avoid dairy for a year, and then gradually add that back into the diet with good results. "Often, that will work, so I don’t even test for lactose intolerance initially," he said.

Despite all the possible etiologies for nonresponsive celiac disease, gluten exposure was found in more than a third of cases, while "true refractory celiac disease really makes up only about 10% or 11% of these nonresponsive patients," said Dr. Murray, referring to a study on the topic (Clin. Gastroenterol. Hepatol. 2007;5:445-50).

Patients with celiac disease also can have multifocal strictures in the proximal duodenum that reach the jejunum, "but rarely affect the ileum," according to Dr. Murray.

Possible lymphomas

"The first thing that I think about when I see a really sick patient previously diagnosed with celiac disease several years before is, ‘Does the patient have lymphoma?’" said Dr. Murray. Ulcerative jejunoileitis typically indicates that lymphoma is imminent, although shallower ulcers are often linked to the use of NSAIDs, he said.

Giant cavitating lymphadenopathy, while rare, is also a consideration, according to Dr. Murray. "A premalignant type of disorder, sometimes will respond to immunosuppressives, but often can presage the development of lymphoma," he said.

True refractory celiac disease involves symptomatic malabsorption, severe enteropathy, and a primary or secondary nonresponse to a gluten-free diet. "By definition, there should be no lymphoma," said Dr. Murray.

Refractory celiac disease is either characterized as type 1, which has a normal T-cell population and responds well to immunosuppression, or as type 2 with clonal T cells.

Dr. Murray said he often uses topical budesonide to treat type 1 patients, with good results, since there is about a 90% recovery rate in this patient population. Type 2 is the most pernicious, with nearly half of patients dying within 5 years of diagnosis, either from malignant or infectious complications, according to Dr. Murray. "Type 2 refractory disease is not a trivial disease," he said.

Although most adults with celiac disease don’t heal, many are asymptomatic; however, this does not mean a patient’s risk of mortality from the disease has improved. Patients are also at greater risk for malignant complications. (Am. J. Gastroenterol. 2010;105:1412-20 [doi:10.1038/ajg.2010.10]).

"We really don’t know what we should do about those asymptomatic patients," said Dr. Murray. He noted that, "Failure to heal is not entirely benign, but it’s not refractory celiac disease," said Dr. Murray.

Dr. Murray stated that he had no disclosures.

wmcknight@frontlinemedcom.com

HOLLYWOOD, FLA. – Refractory celiac disease is often the result of patients having either received an incorrect diagnosis, or their noncompliance, according to Dr. Joseph Murray of the Mayo Clinic in Rochester, Minn.

"When faced with such a patient, it’s important to reconfirm the original diagnosis," said Dr. Murray, who made his remarks during a clinical track presentation at a conference on inflammatory bowel.

In cases in which the diagnosis can be confirmed and the patient is compliant, discovering if there are other conditions, and whether to intervene and how, are the important next steps, according to Dr. Murray.

When patients present with symptoms of nonresponsive celiac disease, besides taking the patient’s history, which should include whether the patient has any first-degree family members with "true" celiac disease, not just family members who have chosen to stop eating gluten, "I will always ask for the original biopsies," said Dr. Murray.

In addition, original serology tests, if they were done, can confirm whether there are celiac-specific antibodies. "Gliadin antibodies are not celiac specific," said Dr. Murray. "You can get gliadin antibodies in virtually every other disorder that affects the intestines, so they are pretty much worthless." Better specificity comes from tissue transglutaminase or endomysial antibodies, he said at the meeting diseases sponsored by the Crohn’s & Colitis Foundation of America.

Human leukocyte antigen genotyping, and whether the patient had a clinically obvious response to a gluten-free diet also will help the clinician puzzle out if the original diagnosis was correct, according to Dr. Murray. Worth noting is whether the patient has dermatitis herpetiformis, "That’s pathognomonic for celiac disease," said Dr. Murray.

For example, in the case of a 90-year-old woman whose biopsy 10 years before had been interpreted as presumptive celiac disease and who had had an initial response to a gluten-free diet, had symptoms that persisted for a decade because she’d contracted tropical sprue from annual visits to Indonesia that were not noted in her original patient history. Treated properly, her symptoms abated entirely, according to Dr. Murray. "She wasn’t exactly happy about her 10 years of living gluten free," he said.

Dangers of noncompliance

As for patients who claim to follow a gluten-free diet, "That’s not true most of the time," said Dr. Murray. "A positive serology test in a patient who’s been following a gluten-free diet for a year or more means they’re not just getting a little gluten. They’re getting a lot of gluten." It can either be advertent or inadvertently, he said.

However, serology is insensitive for lower levels of gluten contamination, but a gram of gluten, roughly one-half a slice of bread per day, can be detected, according to Dr. Murray.

If noncompliance is the reason for the refractory condition, patients are at greater risk for increased mortality, osteoporosis, lymphomas, and other cancers, and psychological effects such as depression. "Eliminating the gluten may take time. Often we have to use behavioral counselors to help," said Dr. Murray.

Also key is to stay in touch with the patient. "Follow-up in patients with celiac disease is abysmal," Dr. Murray said, "It’s almost like once the disease is diagnosed, it’s forgotten about medically."

"The complicating thing about celiac disease can be that autoimmune disorders and like disorders hang out together," said Dr. Murray. "Complications of celiac disease also can occur in multiples."

Bacterial overgrowth, microscopic colitis, lymphoma, and systemic sclerosis associated–dysmotility are all concurrent conditions Dr. Murray reported seeing in his own practice when treating refractory celiac disease.

Because lactose intolerance is also common in celiac disease, Dr. Murray said he will often advises patients to avoid dairy for a year, and then gradually add that back into the diet with good results. "Often, that will work, so I don’t even test for lactose intolerance initially," he said.

Despite all the possible etiologies for nonresponsive celiac disease, gluten exposure was found in more than a third of cases, while "true refractory celiac disease really makes up only about 10% or 11% of these nonresponsive patients," said Dr. Murray, referring to a study on the topic (Clin. Gastroenterol. Hepatol. 2007;5:445-50).

Patients with celiac disease also can have multifocal strictures in the proximal duodenum that reach the jejunum, "but rarely affect the ileum," according to Dr. Murray.

Possible lymphomas

"The first thing that I think about when I see a really sick patient previously diagnosed with celiac disease several years before is, ‘Does the patient have lymphoma?’" said Dr. Murray. Ulcerative jejunoileitis typically indicates that lymphoma is imminent, although shallower ulcers are often linked to the use of NSAIDs, he said.

Giant cavitating lymphadenopathy, while rare, is also a consideration, according to Dr. Murray. "A premalignant type of disorder, sometimes will respond to immunosuppressives, but often can presage the development of lymphoma," he said.

True refractory celiac disease involves symptomatic malabsorption, severe enteropathy, and a primary or secondary nonresponse to a gluten-free diet. "By definition, there should be no lymphoma," said Dr. Murray.

Refractory celiac disease is either characterized as type 1, which has a normal T-cell population and responds well to immunosuppression, or as type 2 with clonal T cells.

Dr. Murray said he often uses topical budesonide to treat type 1 patients, with good results, since there is about a 90% recovery rate in this patient population. Type 2 is the most pernicious, with nearly half of patients dying within 5 years of diagnosis, either from malignant or infectious complications, according to Dr. Murray. "Type 2 refractory disease is not a trivial disease," he said.

Although most adults with celiac disease don’t heal, many are asymptomatic; however, this does not mean a patient’s risk of mortality from the disease has improved. Patients are also at greater risk for malignant complications. (Am. J. Gastroenterol. 2010;105:1412-20 [doi:10.1038/ajg.2010.10]).

"We really don’t know what we should do about those asymptomatic patients," said Dr. Murray. He noted that, "Failure to heal is not entirely benign, but it’s not refractory celiac disease," said Dr. Murray.

Dr. Murray stated that he had no disclosures.

wmcknight@frontlinemedcom.com

HOLLYWOOD, FLA. – Refractory celiac disease is often the result of patients having either received an incorrect diagnosis, or their noncompliance, according to Dr. Joseph Murray of the Mayo Clinic in Rochester, Minn.

"When faced with such a patient, it’s important to reconfirm the original diagnosis," said Dr. Murray, who made his remarks during a clinical track presentation at a conference on inflammatory bowel.

In cases in which the diagnosis can be confirmed and the patient is compliant, discovering if there are other conditions, and whether to intervene and how, are the important next steps, according to Dr. Murray.

When patients present with symptoms of nonresponsive celiac disease, besides taking the patient’s history, which should include whether the patient has any first-degree family members with "true" celiac disease, not just family members who have chosen to stop eating gluten, "I will always ask for the original biopsies," said Dr. Murray.

In addition, original serology tests, if they were done, can confirm whether there are celiac-specific antibodies. "Gliadin antibodies are not celiac specific," said Dr. Murray. "You can get gliadin antibodies in virtually every other disorder that affects the intestines, so they are pretty much worthless." Better specificity comes from tissue transglutaminase or endomysial antibodies, he said at the meeting diseases sponsored by the Crohn’s & Colitis Foundation of America.

Human leukocyte antigen genotyping, and whether the patient had a clinically obvious response to a gluten-free diet also will help the clinician puzzle out if the original diagnosis was correct, according to Dr. Murray. Worth noting is whether the patient has dermatitis herpetiformis, "That’s pathognomonic for celiac disease," said Dr. Murray.

For example, in the case of a 90-year-old woman whose biopsy 10 years before had been interpreted as presumptive celiac disease and who had had an initial response to a gluten-free diet, had symptoms that persisted for a decade because she’d contracted tropical sprue from annual visits to Indonesia that were not noted in her original patient history. Treated properly, her symptoms abated entirely, according to Dr. Murray. "She wasn’t exactly happy about her 10 years of living gluten free," he said.

Dangers of noncompliance

As for patients who claim to follow a gluten-free diet, "That’s not true most of the time," said Dr. Murray. "A positive serology test in a patient who’s been following a gluten-free diet for a year or more means they’re not just getting a little gluten. They’re getting a lot of gluten." It can either be advertent or inadvertently, he said.

However, serology is insensitive for lower levels of gluten contamination, but a gram of gluten, roughly one-half a slice of bread per day, can be detected, according to Dr. Murray.

If noncompliance is the reason for the refractory condition, patients are at greater risk for increased mortality, osteoporosis, lymphomas, and other cancers, and psychological effects such as depression. "Eliminating the gluten may take time. Often we have to use behavioral counselors to help," said Dr. Murray.

Also key is to stay in touch with the patient. "Follow-up in patients with celiac disease is abysmal," Dr. Murray said, "It’s almost like once the disease is diagnosed, it’s forgotten about medically."

"The complicating thing about celiac disease can be that autoimmune disorders and like disorders hang out together," said Dr. Murray. "Complications of celiac disease also can occur in multiples."

Bacterial overgrowth, microscopic colitis, lymphoma, and systemic sclerosis associated–dysmotility are all concurrent conditions Dr. Murray reported seeing in his own practice when treating refractory celiac disease.

Because lactose intolerance is also common in celiac disease, Dr. Murray said he will often advises patients to avoid dairy for a year, and then gradually add that back into the diet with good results. "Often, that will work, so I don’t even test for lactose intolerance initially," he said.

Despite all the possible etiologies for nonresponsive celiac disease, gluten exposure was found in more than a third of cases, while "true refractory celiac disease really makes up only about 10% or 11% of these nonresponsive patients," said Dr. Murray, referring to a study on the topic (Clin. Gastroenterol. Hepatol. 2007;5:445-50).

Patients with celiac disease also can have multifocal strictures in the proximal duodenum that reach the jejunum, "but rarely affect the ileum," according to Dr. Murray.

Possible lymphomas

"The first thing that I think about when I see a really sick patient previously diagnosed with celiac disease several years before is, ‘Does the patient have lymphoma?’" said Dr. Murray. Ulcerative jejunoileitis typically indicates that lymphoma is imminent, although shallower ulcers are often linked to the use of NSAIDs, he said.

Giant cavitating lymphadenopathy, while rare, is also a consideration, according to Dr. Murray. "A premalignant type of disorder, sometimes will respond to immunosuppressives, but often can presage the development of lymphoma," he said.

True refractory celiac disease involves symptomatic malabsorption, severe enteropathy, and a primary or secondary nonresponse to a gluten-free diet. "By definition, there should be no lymphoma," said Dr. Murray.

Refractory celiac disease is either characterized as type 1, which has a normal T-cell population and responds well to immunosuppression, or as type 2 with clonal T cells.

Dr. Murray said he often uses topical budesonide to treat type 1 patients, with good results, since there is about a 90% recovery rate in this patient population. Type 2 is the most pernicious, with nearly half of patients dying within 5 years of diagnosis, either from malignant or infectious complications, according to Dr. Murray. "Type 2 refractory disease is not a trivial disease," he said.

Although most adults with celiac disease don’t heal, many are asymptomatic; however, this does not mean a patient’s risk of mortality from the disease has improved. Patients are also at greater risk for malignant complications. (Am. J. Gastroenterol. 2010;105:1412-20 [doi:10.1038/ajg.2010.10]).

"We really don’t know what we should do about those asymptomatic patients," said Dr. Murray. He noted that, "Failure to heal is not entirely benign, but it’s not refractory celiac disease," said Dr. Murray.

Dr. Murray stated that he had no disclosures.

wmcknight@frontlinemedcom.com

HOLLYWOOD, FLA. – The relative risk of thromboembolic events is greater in inpatient inflammatory bowel disease patients than in the general population, but prophylactic treatment is still not standard, according to a speaker at a conference on inflammatory bowel diseases.

"It’s a relatively rare problem, only about 1 to 1.5 percent," said Dr. Athos Bousvaros, of Boston Children’s Hospital. "So, why worry about it so much? Because it really is a major source of morbidity in the IBD population. It usually happens in the sick patients, the ones at risk for strokes; and it usually happens at the worst time, when you’re thinking about colectomy."

However, Dr. Bousvaros said only about a third of IBD patients at risk for a thromboembolic event are given prophylactic treatment in the inpatient setting, especially in severe colitis, and it is generally recommended.

Although pharmacologic prophylaxis is included in the American College of Gastroenterology guidelines, Dr. Bousvaros cited a recent study that found only 35% of gastroenterologists in the United States actually do so (J. Clin. Gastroenterol. 2013;47:e1-e6).

"In the inpatient setting, especially in severe colitis, [prophylaxis] is generally recommended," Dr. Bousvaros said. "It is included in the AGA [American Gastroenterological Association] physician performance measure set." In the outpatient setting, data do not support it, he said.

Relative risk high

While the absolute risk is low, the relative risk of a venous thromboembolic event is six times greater in IBD, particularly in patients aged 20 years or less, said Dr. Bousvaros, citing a cohort study that used Danish administrative data (Gut 2011;60:937-43). "It’s mainly patients with flares, and mainly those with colitis, either Crohn’s or severe ulcerative colitis," Dr. Bousvaros said.

In a prospective study of about 2,800 IBD patients (mean age, 42 years) recruited over 2.5 years, matched with non-IBD controls, and followed for several years, about 4% developed de novo venous thromboembolism (Gastroenterol. 2010;139:779-787.e1). Dr. Bousvaros emphasized that IBD was an independent risk factor for VTE recurrence in the study. "They were typically treated with long-standing prophylaxis. And if any anticoagulation was involved, the risk of recurrence was high," he said at the meeting, which was sponsored by the Crohn’s & Colitis Foundation of America.

High-risk criteria

Overall, the relative risk for VTE was found by a just-published meta-analysis of more than 200,000 IBD patients to be 2.4 for deep vein thrombosis, 2.5 for pulmonary embolism, 1.3 for ischemic heart disease, and 3.4 for mesenteric ischemia (J. Crohns Colitis 2013 Oct 29 [doi: 10.1016/j.crohns.2013.09.021]). Dr. Bousvaros said the investigators did not find an increased risk for arterial thromboembolic events in IBD, but that VTEs "were highly significant in this population."

Patients with IBD should be considered high risk for VTE if they are being treated in hospital for severe colitis and have a personal or family history of thrombosis, have known thrombophilia, have been taking oral contraceptives, have a history of smoking, are obese, or have had a PICC line.

"Any of those makes you a particularly high-risk patient," Dr. Bousvaros said.

Dr. Bousvaros disclosed he has consulting relationships with Cubist, Dyax, and Millennium.

wmcknight@frontlinemedcom.com

HOLLYWOOD, FLA. – The relative risk of thromboembolic events is greater in inpatient inflammatory bowel disease patients than in the general population, but prophylactic treatment is still not standard, according to a speaker at a conference on inflammatory bowel diseases.

"It’s a relatively rare problem, only about 1 to 1.5 percent," said Dr. Athos Bousvaros, of Boston Children’s Hospital. "So, why worry about it so much? Because it really is a major source of morbidity in the IBD population. It usually happens in the sick patients, the ones at risk for strokes; and it usually happens at the worst time, when you’re thinking about colectomy."

However, Dr. Bousvaros said only about a third of IBD patients at risk for a thromboembolic event are given prophylactic treatment in the inpatient setting, especially in severe colitis, and it is generally recommended.

Although pharmacologic prophylaxis is included in the American College of Gastroenterology guidelines, Dr. Bousvaros cited a recent study that found only 35% of gastroenterologists in the United States actually do so (J. Clin. Gastroenterol. 2013;47:e1-e6).

"In the inpatient setting, especially in severe colitis, [prophylaxis] is generally recommended," Dr. Bousvaros said. "It is included in the AGA [American Gastroenterological Association] physician performance measure set." In the outpatient setting, data do not support it, he said.

Relative risk high

While the absolute risk is low, the relative risk of a venous thromboembolic event is six times greater in IBD, particularly in patients aged 20 years or less, said Dr. Bousvaros, citing a cohort study that used Danish administrative data (Gut 2011;60:937-43). "It’s mainly patients with flares, and mainly those with colitis, either Crohn’s or severe ulcerative colitis," Dr. Bousvaros said.

In a prospective study of about 2,800 IBD patients (mean age, 42 years) recruited over 2.5 years, matched with non-IBD controls, and followed for several years, about 4% developed de novo venous thromboembolism (Gastroenterol. 2010;139:779-787.e1). Dr. Bousvaros emphasized that IBD was an independent risk factor for VTE recurrence in the study. "They were typically treated with long-standing prophylaxis. And if any anticoagulation was involved, the risk of recurrence was high," he said at the meeting, which was sponsored by the Crohn’s & Colitis Foundation of America.

High-risk criteria

Overall, the relative risk for VTE was found by a just-published meta-analysis of more than 200,000 IBD patients to be 2.4 for deep vein thrombosis, 2.5 for pulmonary embolism, 1.3 for ischemic heart disease, and 3.4 for mesenteric ischemia (J. Crohns Colitis 2013 Oct 29 [doi: 10.1016/j.crohns.2013.09.021]). Dr. Bousvaros said the investigators did not find an increased risk for arterial thromboembolic events in IBD, but that VTEs "were highly significant in this population."

Patients with IBD should be considered high risk for VTE if they are being treated in hospital for severe colitis and have a personal or family history of thrombosis, have known thrombophilia, have been taking oral contraceptives, have a history of smoking, are obese, or have had a PICC line.

"Any of those makes you a particularly high-risk patient," Dr. Bousvaros said.

Dr. Bousvaros disclosed he has consulting relationships with Cubist, Dyax, and Millennium.

wmcknight@frontlinemedcom.com

HOLLYWOOD, FLA. – The relative risk of thromboembolic events is greater in inpatient inflammatory bowel disease patients than in the general population, but prophylactic treatment is still not standard, according to a speaker at a conference on inflammatory bowel diseases.

"It’s a relatively rare problem, only about 1 to 1.5 percent," said Dr. Athos Bousvaros, of Boston Children’s Hospital. "So, why worry about it so much? Because it really is a major source of morbidity in the IBD population. It usually happens in the sick patients, the ones at risk for strokes; and it usually happens at the worst time, when you’re thinking about colectomy."

However, Dr. Bousvaros said only about a third of IBD patients at risk for a thromboembolic event are given prophylactic treatment in the inpatient setting, especially in severe colitis, and it is generally recommended.

Although pharmacologic prophylaxis is included in the American College of Gastroenterology guidelines, Dr. Bousvaros cited a recent study that found only 35% of gastroenterologists in the United States actually do so (J. Clin. Gastroenterol. 2013;47:e1-e6).

"In the inpatient setting, especially in severe colitis, [prophylaxis] is generally recommended," Dr. Bousvaros said. "It is included in the AGA [American Gastroenterological Association] physician performance measure set." In the outpatient setting, data do not support it, he said.

Relative risk high

While the absolute risk is low, the relative risk of a venous thromboembolic event is six times greater in IBD, particularly in patients aged 20 years or less, said Dr. Bousvaros, citing a cohort study that used Danish administrative data (Gut 2011;60:937-43). "It’s mainly patients with flares, and mainly those with colitis, either Crohn’s or severe ulcerative colitis," Dr. Bousvaros said.

In a prospective study of about 2,800 IBD patients (mean age, 42 years) recruited over 2.5 years, matched with non-IBD controls, and followed for several years, about 4% developed de novo venous thromboembolism (Gastroenterol. 2010;139:779-787.e1). Dr. Bousvaros emphasized that IBD was an independent risk factor for VTE recurrence in the study. "They were typically treated with long-standing prophylaxis. And if any anticoagulation was involved, the risk of recurrence was high," he said at the meeting, which was sponsored by the Crohn’s & Colitis Foundation of America.

High-risk criteria

Overall, the relative risk for VTE was found by a just-published meta-analysis of more than 200,000 IBD patients to be 2.4 for deep vein thrombosis, 2.5 for pulmonary embolism, 1.3 for ischemic heart disease, and 3.4 for mesenteric ischemia (J. Crohns Colitis 2013 Oct 29 [doi: 10.1016/j.crohns.2013.09.021]). Dr. Bousvaros said the investigators did not find an increased risk for arterial thromboembolic events in IBD, but that VTEs "were highly significant in this population."

Patients with IBD should be considered high risk for VTE if they are being treated in hospital for severe colitis and have a personal or family history of thrombosis, have known thrombophilia, have been taking oral contraceptives, have a history of smoking, are obese, or have had a PICC line.

"Any of those makes you a particularly high-risk patient," Dr. Bousvaros said.

Dr. Bousvaros disclosed he has consulting relationships with Cubist, Dyax, and Millennium.

wmcknight@frontlinemedcom.com