Misdiagnosis, noncompliance often culprits in refractory celiac disease

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.

Thrombosis precautions in IBD not met in two-thirds of high-risk cases

HOLLYWOOD, FLA. (FRONTLINE MEDICAL NEWS) – 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.

Bariatric surgery benefits in type 2 diabetes linked to disease duration

MELBOURNE (FRONTLINE MEDICAL NEWS) – The benefits of bariatric surgery in people with type 2 diabetes are significantly reduced with longer disease duration at the time of surgery and with time since surgery, a long-running, prospective, controlled study has found. The Swedish Obese Subjects study showed that 72% of surgery patients achieved remission at 2 years after treatment, compared with 16% of control patients. Furthermore, 15 years after surgery, 31% of the surgery patients remained in remission, compared to 7% of control patients, according to data presented at the International Diabetes Federation world congress. When stratified by disease duration at baseline, newly diagnosed patients maintained significantly higher remission rates at 2, 10 and 15 years’ follow-up (roughly 94%, 60%, and 47%, respectively) than did those who had had diabetes for more than 3 years at baseline (about 39%, 12%, and 9%). These data came from the SOS (Swedish Obese Subjects) study, a nonrandomized, prospective, observational study involving 2,010 obese subjects who underwent bariatric surgery in 1987-2001, when they were 37-60 years old. A total of 68% of the bariatric surgery recipients had vertical band gastroplasty, 19% underwent gastric banding, and 13% had a Roux en-Y gastric bypass. They were extensively matched by 18 variables to 2,037 obese controls. The SOS study is being conducted at 25 surgical departments and 480 primary care clinics across Sweden. Follow-up is ongoing. There were 343 individuals with type 2 diabetes in the surgical group and 260 in the control group, enabling a secondary analysis of the impact of bariatric surgery in type 2 diabetes. Presenter Markku Peltonen said that although bariatric surgery achieves impressive results in the short-term, there is considerable relapse in the longer term. “It’s typical of bariatric surgery that you achieve the greatest weight loss initially, after 2 years, then there is a slow regain again and this was observed in this study,” said Dr. Peltonen, director of the department of chronic disease prevention at the National Institute for Health and Welfare, Helsinki. “Even in the long term, they are doing much better than the controls who were treated with traditional weight management means,” he said in an interview. This also extended to the microvascular and macrovascular complications of diabetes, with the study showing a significant 47% lower incidence of complications in the surgery group, compared with the control group. However, these benefits were also attenuated by disease duration. Patients who had had diabetes for more than 3 years and were treated with surgery showed no significant differences in diabetes complication rates, compared with the patients given medical care only. Dr. Peltonen said he was surprised by the degree of impact that disease duration had on the outcomes of surgery. “Somehow the expectation would be that we would see an effect even in those people with long diabetes duration, because they have a serious, advanced disease but it looks like, based on our results, that maybe it’s so that the disease has advanced for so long that bariatric surgery cannot reverse that development.” Session chair John Dixon said the SOS study represented the pinnacle of long-term data for bariatric surgery, and offered impressive insights. “The fact that 31% of these patients are still in remission from diabetes some 15 years down the track is extraordinary, because we know the deterioration of beta cells is significant and this group has held it off for a long time,” said Dr. Dixon, head of clinical obesity research at the Baker IDI Heart and Diabetes Institute in Melbourne. Dr. Dixon said the finding that patients treated early fared better and had a reduction in long-term complications was also a very important clinical finding, suggesting that bariatric surgery should be considered earlier in obese patients not getting good control with conventional therapy. SOS was supported by the Swedish Research Council, the Swedish Foundation for Strategic Research, and the Swedish government. Some study investigators authors had received paid lectureships, held stock in, or were on the advisory boards for pharmaceutical companies.