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SKEPTOID BLOG:

Does A New Test Accurately Diagnose Irritable Bowel Syndrome?

by Stephen Propatier

May 29, 2015

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Donate National news media outlets are reporting a breakthrough in the diagnosis and treatment of irritable bowel syndrome (IBS). Dr. Mark Pimentel, from the Cedars-Sinai Medical Center of Los Angeles, believes he has discovered a method to diagnose the disease using a pair of blood tests that he has developed. These tests are a creative attempt to streamline the diagnostic process for IBS and provide clinicians with a new tool to help treat the disease. This sounds like a perfect medical solution, but is it?

A simple laboratory blood test is the holy grail for most disease diagnosis. Very few medical problems actually offer such a simple diagnostic tool. Since irritable bowel syndrome is a complicated and controversial diagnosis of exclusion I was rather surprised to see a blood test as the answer. Let's take a close look at this exciting research and parse out the facts.

The study was published in PLOS ONE, a public science journal published online. Titled "Development and Validation of a Biomarker for Diarrhea-Predominant Irritable Bowel Syndrome in Human Subjects," it was a relatively large multi-center trial. Study participants previously diagnosed with IBS by one of the the current techniques, called the Rome Criteria, were then randomized. Researchers used two independent blood tests to evaluate the level of an antibody called anti-vinculin and anti-CdtB antibodies. The study is a little complicated on the finer points of how this is diagnostic for IBS. I will try to simplify this although it will not be 100% technically accurate on a bio-molecular level.

These two antibodies are created by our body in response to a few types of intestinal bacterial infection. The bacteria they test for generate an endotoxin at levels high enough to inflame and damage the lining of our gut. After exposure our body creates antibodies to attack the toxin if it ever appears again. The researchers have found in animal models that elevated levels of the antibodies seem to inflame the gut lining. They believe that a normal gut structural protein is close enough to the structure of the toxin that the antibodies are triggering an autoimmune attack on the gut. Simply put, you get sick with a stomach bug, your body builds defenses, and by a quirk of chance those defenses misidentify normal bowel tissue as an infection toxin. The defenses attack your gut and produce all the symptoms.

Although it's a plausible hypothesis there are several unstated premises in this line of reasoning, including a tautological error. The facts seem to be lost in the published reports both by the press and the author. They both give the probably false impression that this study has both determined the cause for IBS and produced a definitive diagnostic test. The published research (as usual) paints a far more accurate and conservative evaluation of what this research means.

In their abstract, the researchers write:
Anti-vinculin and anti-CdtB antibodies also appear part of the pathophysiology of post-infectious IBS and may identify a subgroup of D-IBS for directed therapies. Most importantly, this appears to be an important step in determining organic bases for IBS.
For news outlets to be correct, a basic question must be answered first: What is the cause of IBS? This is an important question, both for the disease and the test. IBS is by definition a syndrome, meaning a set of correlated medical symptoms. IBS is a group of symptoms that are collectively similar. Irritable bowel syndrome is a description of a the end result and is not a description of a cause. To call a test diagnostic you have to know if it is checking for the cause. This is the tautological error the author is making in public promotion. He is leaving out a key supposition. He believes that this test will check for the presence of these antibodies. He also believes that these antibodies are the cause of IBS, but are they?

A good diagnostic test must have two attributes to be effective: specificity and sensitivity. A perfect predictor would be described as 100% sensitive (i.e. predicting all people from the sick group as sick) and 100% specific (i.e. not predicting anyone from the healthy group as sick); however, theoretically any predictor will possess a minimum error bound known as the Bayes error rate.

Let's take a look at a common very reliable reliable diagnostic labs test and compare it to this IBS test. Strep throat has a reasonably reliable test. We know definitively the bacteria that causes the disease. We have a 95% sensitivity test with a high specificity, meaning that if you have a positive culture you have strep throat and if you have a negative culture there is only a 5% possibility that it is missed. Those numbers are about as good as it gets in the real world. How do these two IBS tests compare to the throat culture? The short answer is... not very well, for several really significant reasons.

We have a clearly understood and detectable cause for strep throat, but is there a similarly clear, detectable cause for IBS? A test that correlates well with diagnosed IBS is really not proof. The cause or causes of IBS are far from settled by this one bit of lab work. Traditionally, the focus of diagnosing IBS has been on alterations in gastrointestinal motility and on visceral hypersensitivity. More recent studies have considered the role of inflammation, alterations in fecal flora, and bacterial overgrowth. The role of food sensitivity and genetics are also being considered.

Here's what researchers understand as the current consensus for IBS:

?It's a gastrointestinal disorder characterized by chronic abdominal pain and altered bowel habits in the absence of an identified cause. The pathophysiology of IBS remains uncertain.

?Although motor abnormalities of the gastrointestinal tract (increased frequency and irregularity of luminal contractions, abnormal transit time) are detectable in some patients with IBS, no predominant pattern has emerged as a marker for IBS.

?Selective hypersensitization of visceral afferent nerves in the gut has been observed in patients with IBS and is one explanation for IBS symptoms.

?Immunohistologic investigation has revealed mucosal immune system activation characterized by alterations in particular immune cells and markers in some patients with IBS.

?The development of IBS following infectious gastroenteritis has been suspected clinically based upon a history of an acute diarrheal illness preceding the onset of irritable bowel symptoms in some patients. The cause of bowel symptoms following acute infection is uncertain although several theories (malabsorption, increased enteroendocrine cells/lymphocytes, and antibiotic use) have been proposed.

?The complex ecology of the fecal microflora has led to speculation whether changes in its composition could be associated with IBS.

?The role of food in the pathophysiology of IBS is not clear. Investigations have centered on the development of food specific antibodies, carbohydrate malabsorption, and gluten sensitivity.

?A genetic susceptibility to IBS is suggested by several twin studies, although familial patterns may also reflect underlying social factors. Associations between specific genes and IBS are under investigation.

?Psychosocial factors may influence the expression of IBS symptoms.

So you can see above that dismissing all this other research due to this one study is problematic. IBS may not be one disease; it may in fact be a set of multiple causes that all present with similar symptoms or complaints. It may be a combination of all these factors. It is unlikely that one test, checking one aspect of the disease, is a sufficient diagnostic standard. What if sufferers have never had the specific bacterial infections? Does that mean sufferers now don't have IBS or are we saying that they had it and don't know it?

Let's go back to our strep throat example. Strep throat has a well-defined cause that is consistently found in the afflicted. IBS just doesn't have that. Although checking people for the presence of antibody sounds convincing, there is no consensus that IBS is solely an autoimmune disease. So a test for an antibody is hardly testing a definitive cause of IBS. Worse this test is not extremely reliable even within the autoimmune hypothesis.

Comparing it again to strep throat: if streptococcus group A is present in the throat and the sample is cultured properly, there is no chance that the test will be falsely negative (i.e. you have strep throat but the test missed it). In the case of IBS, Dr. Pimentel's tests are both 90% or better at finding the antibodies. Yet both tests only had a 44% match rate with people diagnosed previously with IBS. You read that right: there is less than a 50/50 chance that this test matched with an IBS sufferer.

So how can Dr. Pimentel's opinion that these tests clinically diagnose IBS be accurate? The short answer is that maybe it can, or maybe it can't. There are some unproven assumptions he's glossing over. If all other causes for IBS are wrong, and this test can be refined for to much higher sensitivity, then maybe you will have a definitive test. That's far from having a definitive lab test for diagnosis. Having such an unsupported hypothesis about the cause—and having an unreliable test based on that hypothesis, with a low-yield sensitivity—is hardly redefining the disease, as it has been reported. These two tests are promising but unproven. It may be that we have discovered one piece of the puzzle of IBS. Unfortunately, this is not currently rigorous enough to be a means to include or exclude patients.

The researchers and talking heads all comment about the difficulty in diagnosing IBS. Many sufferers are told that it is psychiatric in nature, meaning that stress or anxiety can cause IBS-type symptoms. This is truly possible. People don't like that type of diagnosis because, for reasons I cannot fathom, psychiatric illness is seen as some type of weakness and not a true illness. This is false. That said, people feel stigmatized in our society because of a stress or anxiety diagnosis. Feeling stigmatized produces significant problems. It is very desirable for both healthcare providers and patients to provide a definitive diagnostic answer for a non-psychiatric cause, otherwise patients will continue to search for a different, more palatable answer, this can subsequently drive people to seek out quackery or other dangerous fringe treatments. Although a proven definitive test for IBS would be wonderful, wide use of an unreliable test will have disastrous results. If the test is only half-reliable and you tell someone falsely that they definitively don't have IBS, it will result in the same mental distress the authors are hoping this type of test will relieve.

Often these test don't pan out over time. But you certainly won't be seeing talking heads correcting the exaggerated claims they're currently making about this diagnostic technique. In the news media they love the hot topic, the new test, the sexy treatment. Authors like attention and embellished or exaggerated findings to help them to get funding. It adds to public confusion and even distress. Always, I mean always, look at news stories about health issues with a skeptical eye. Most of the time they are just plain wrong. They are there to catch your eye and keep your attention. Often the reporting is far away from well-balanced and reasonable advice. If you're getting health information from the 6 o'clock news, you have good reason to be skeptical.

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You can follow me at Twitter @steveproacnp for a daily dose of skeptical nursing. Please check out the completion of the series Occ: The Skeptical Caveman, which I helped produce with the guys at The Skeptics Guide To the Universe.

Disclaimer: This post is my personal opinion, it is not a substitute for medical care. It is for informational purposes only. The information on Skeptoid blog is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. This post does not reflect the opinion of my partners, professional affiliates, or academic affiliations. I have no financial conflicts of interest to disclose.

by Stephen Propatier

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