Crohn's disease news! Cool digestive facts!
Want to keep current on the latest news about Crohn's disease? I invite you to follow this blog. You'll find the latest research on drugs, diet, and other issues related to living with Crohn's. I'll spotlight cool facts about digestion, too.
Watch for a new posting once every week or two. Also, if you'd like to learn more about a lesser-known treatment for Crohn's, take a moment to explore my book, Beat Crohn's! Getting to Remission with Enteral Nutrition. You can see reviews and read a sample on the Barnes & Noble and Amazon websites.
Grin and bear it - June 10, 2015
Patients with Crohn's disease put up with a good deal, but this man seems to have had particularly bad luck. He developed three fistulas on his cheeks (ouch!) (pictures in the link below). They started inside his mouth, in areas inflamed from dental disease, and tunneled their way outward. It took extracting the affected teeth and a course of antibiotics to clear them up.
All I can say is brush your teeth well!
Goel RM, Hullah E. Images in clinical medicine. Orofacial fistulae associated with Crohn's disease. N Engl J Med. 2015 May 28;372(22):e29. doi: 10.1056/NEJMicm1402919.
What to read on the throne - June 3, 2015
As I was browsing the exhibits at Book Expo America, I came across an imprint with a decidedly unusual niche: books designed for use while otherwise occupied. The plump, softcover compendiums, suitably titled Uncle John's Bathroom Readers, contain anecdotes, trivia, and cornball humor of an appropriate length for a quick visit to the loo. The audience is clearly loyal: Not only is the twenty-eighth annual Bathroom Reader due out this year, but there's an annual version just for children as well. (The intriguing 2014 entrant was Uncle John's iFlush: Hurtling Thru History Bathroom Reader for Kids Only.) The compilers of these decidedly different books refer to themselves collectively as the Bathroom Readers' Institute, dedicated "to curing bathroom boredom around the world since 1987." A noble goal!
Extra med equals extra benefit? Maybe not - November 27, 2013
If you are starting Remicaid (infliximab) for Crohn's disease, should you take another immunomodulating drug as well? Opinions differ, and there is no definitive answer. However, here's one study that compares Remicaid plus methotrexate with Remicaid alone.
The 126 patients in the study had all started prednisone recently. They began to taper the steroid and, at the same time, started treatment with either Remicaid plus methotrexate or Remicaid plus a placebo.
The addition of methotrexate was not more effective than using Remicaid alone. After fifty weeks, approximately 30 percent of those in each group had experienced treatment failure (failure to achieve prednisone-free remission at fourteen weeks or failure to maintain remission through fifty weeks).
Feagan BG, McDonald JW, Panaccione R, et al. Methotrexate in combination with infliximab is no more effective than infliximab alone in patients with Crohn's disease. Gastroenterology. 2013 Nov 21. doi:pii: S0016-5085(13)01671-5. 10.1053/j.gastro.2013.11.024. [Epub ahead of print].
The nose knows - October 6, 2013
Of our five senses, it turns out that at least two may be affected by Crohn's disease or ulcerative colitis. A study of fifty-nine patients with IBD found that more than half (57.6%) had a reduced sense of smell (compared with healthy individuals and published norms). In addition, nearly a third of the IBDers (30.5%) had a reduced sense of taste. However, the patients themselves weren't conscious that their senses of smell and/or taste were affected.
Steinbach S, Reindl W, Dempfle A, et al. Smell and taste in inflammatory bowel disease. PLoS One. 2013 Sep 25;8(9):e73454.
Six of one, half a dozen of the other - September 15, 2013
Corticosteroids and enteral nutrition were equally effective in children treated at a Canadian hospital. Remission rates were 88.9% in 36 children who received enteral nutrition and 91.3% in 69 who received steroids. Although the children were not randomly assigned to the different treatments (their records were examined retrospectively), the results are comparable to those achieved in several other studies of enteral nutrition in children.
Soo J, Malik BA, Turner JM, et al. Use of exclusive enteral nutrition is just as effective as corticosteroids in newly diagnosed pediatric Crohn's disease. Dig Dis Sci. 2013 Sep 12. [Epub ahead of print]
Inside the tummy of a king - September 3, 2013
Breaking news: Richard the Third had a bellyful of roundworms. These little critters travel in feces, so either human waste was used to compost the king's vegetable garden or his cook didn't wash up after using the privy. All in all, there is something to be said for modern standards of hygiene.
Source: PD Mitchell, HY Yeh, J. Appleby, R Buckley. The intestinal parasites of King Richard III. Lancet. 2013 September 4.
Vedolizumab for Crohn's disease - August 25, 2013
Results were just released from a study of vedolizumab, the newest biologic in development for the treatment of Crohn's disease. The drug's effectiveness was modest. In a placebo-controlled induction phase, 14.5% of patients who received vedolizumab and 6.8% of those who received a placebo were in remission at six weeks after being treated at zero and two weeks. The percentage of responders (that is, patients who improved but did not reach remission) did not differ significantly between the vedolizumab and placebo groups.
A more extended trial included 461 patients who had responded to vedolizumab after six weeks of treatment but had not necessarily reached remission. They were randomly assigned to continue treatment until the end of a year with vedolizumab every four weeks, vedolizumab every six weeks, or a placebo. After 52 weeks, remission rates were 21.6% with placebo, 36.4% with vedolizumab every eight weeks, and 39.0% with vedolizumab every four weeks. The improvement in both of the active treatment groups was significantly better than with the placebo. That said, remember that only responders were entered in the longer phase of the trial, so remission rates in the overall population of patients with Crohn's disease would be lower than the 36% to 39% achieved among the responders.
As far as one can generalize from these results, infliximab (Remicaid) remains the most effective of the current or potential biologic drugs in the treatment of Crohn's disease. However, extra options for those who have run through the existing ones are welcome.
Source: WJ Sandborn, BG Feagan, P Rutgeerts, et al. for the GEMINI 2 Study Group. Vedolizumab as induction and maintenance therapy for Crohn's disease. N Engl J Med 2013 August 22; 369:711-721.Secrets of the sloth - July 30, 2013
The humble sloth has quite peculiar digestive habits, as I learned on a visit to the National Aviary in Pittsburgh. It poops only once a week or so, descending to the ground to do so. The rest of the time, it lounges comfortably in a tree.
Since the sloth's food of choice is tree leaves, which are tough for gut bacteria to ferment, digestion is a slow, slow process. When the animal is cold, during the night or a rainy day, its rate of digestion decreases. In contrast, sunbathing speeds up the digestive process. (Human digestion, as far as I know, is not enhanced by a trip to the beach!) Here's a great short video of the National Aviary's sloth, Wookie.
Source: Jacalyn Giacalone, "Sloths: Two-toed, Choloepus hoffmanni; Three-toed, Bradypus variegatus," available at http://www.montclair.edu/csam/prism/rainforest-connection/panama/mammal-directory/sloths/.
Enteral nutrition for adults - July 18, 2013
Most of the recent studies of enteral nutrition (EN) have been performed in children. Therefore it's nice to see a new study in adults, especially one with very positive results. Health-related quality of life, including bowel symptoms, systemic symptoms, social function, and emotional status, improved significantly after four weeks of treatment with EN. Eleven of 13 patients (85%) reached remission. Eight said they would be willing to use EN again if they relapsed.
Source: Guo Z, Wu R, Zhu W, et al. Effect of Exclusive enteral nutrition on health-related quality of life for adults with active Crohn's disease. Nutr Clin Pract. 2013 Jul 12. [Epub ahead of print]
Expanding options - May 19, 2013
Some intestinal strictures are caused by temporary inflammation; they respond to steroids or enteral nutrition. But other strictures become thick and rigid ("fibrotic"). These have to be cut out surgically (although occasionally they can be stretched open instead, with a little balloon attached to the end of an endoscope). Now there's a potential, although still-experimental, third option: biodegradable stents.
What are they? Well, you've probably heard of stents being used for people with blocked arteries from cardiovascular disease. This is the same sort of thing—a hollow tube—but inserted into a length of intestine (instead of into an artery) to widen the strictured channel and keep it open. The stent is designed to degrade on its own and ultimately disappear, reducing the risk that it will become displaced and cause problems elsewhere in the intestines.
In the case reported, a biodegradable stent was used to treat a long stricture. The patient had immediate relief from the obstructive symptoms. The area where the stricture had been was still open sixteen months later, although the stent itself had dissolved. I will be eager to hear of more experiments with this promising technique.
Source: Rodrigues C, Oliveira A, Santos L, et al. Biodegradable stent for the treatment of a colonic stricture in Crohn's disease. World J Gastrointest Endosc. 2013 May 16;5(5):265-9.
Accutane and IBD - May 12, 2013
Here's some good news for those suffering from acne. Although there has been some speculation that using isotretinoin (Accutane) could raise the risk of developing ulcerative colitis or Crohn's disease, a large case-control study suggests the contrary. Among women aged 18 to 46, isotretinoin use was not associated with an increased risk of IBD. A meta-analysis of five studies of isotretinoin and IBD did not show an increased risk of IBD either.
Source: Etminan M, Bird ST, Delaney JA, et al. Isotretinoin and risk for inflammatory bowel disease: a nested case-control study and meta-analysis of published and unpublished data. JAMA Dermatol. 2013 Feb;149(2):216-20.
It's not all or nothing - April 20, 2013
Typically, using enteral nutrition (EN) to achieve remission from Crohn's disease involves sticking with a full-liquid diet for a few weeks. But it's been clear for years that some patients manage to cheat a bit and yet still achieve remission. In a recently published study, doctors retrospectively examined the records of twenty-three children treated with EN who received 80 to 90 percent of their calories from the liquid formula and the remainder from a normal diet. Among these patients, 65 percent reached remission. This is good news for children (and adults) who would be willing to try EN if they could have a few nibbles of their favorite foods on the side.
Source: Gupta K, Noble A, Kachelries KE, et al. A novel enteral nutrition protocol for the treatment of pediatric Crohn's disease. Inflamm Bowel Dis. 2013 Apr 4. [Epub ahead of print]
Antibiotics as maintenance drugs - March 24, 2013
Using antibiotics to control Crohn's disease is nothing new. Flagyl and, more recently, ciprofloxacin (Cipro) have been used for years to treat abscesses and fistulas. In addition, sulfasalazine (Azulfidine), which contains a sulfa antibiotic, has a decades-long history as a maintenance medication. Now ciprofloxacin has been tested as a maintenance drug in thirty-three patients with Crohn's disease. After undergoing surgery for Crohn's, they were randomized to six months of treatment with ciprofloxacin (500 mg twice daily) or a placebo.
The results were not encouraging. The patients in the two groups were equally likely to have a recurrence of Crohn's disease. Also, those who received the antibiotic experienced a rather high rate of side effects. Nevertheless I am happy to see this study published. It is just as important to know what doesn't work as what does. Otherwise we waste time and money and risk possible harm by using ineffective therapies.
Source: Herfarth HH, Katz JA, Hanauer SB, et al. Ciprofloxacin for the prevention of postoperative recurrence in patients with Crohn's disease: a randomized, double-blind, placebo-controlled pilot study. Inflamm Bowel Dis. 2013 Mar 18. [Epub ahead of print]
Don't blame it on the bottle - March 9, 2013
Among 146,681 women enrolled in the Nurses Health Study, those who were breastfed in infancy and those who weren't were equally likely to develop Crohn's disease in adulthood.
Source: Khalili H, Ananthakrishnan AN, Higuchi LM, et al. Early life factors and risk of inflammatory bowel disease in adulthood. Inflamm Bowel Dis. 2013 Mar 18. [Epub ahead of print]
Picture of a patient - March 3, 2013
This gentleman has Crohn's disease and needed a very extensive resection! The sculpture is by Bruno Catalano.
Crohn's disease in Canada - December 30, 2012
Crohn's disease is more common in northern latitudes, with Sweden and Canada reporting some of the highest rates. According to the latest report, approximately 129,000 Canadians have Crohn's disease, with 5,700 new cases diagnosed each year. When you add in patients with ulcerative colitis, some 233,000 Canadians have IBD. That's one out of every 150 Canadians! Canadian IBDers, you have an impressive potential voting bloc there.
Rocchi A, Benchimol EI, Bernstein CN, et al. Inflammatory bowel disease: a Canadian burden of illness review. Can J Gastroenterol. 2012 Nov;26(11):811-7.
More success with enteral nutrition in Crohn's disease - December 22, 2012
Of thirty-four children with active Crohn's disease, 85 percent reached remission after six weeks of treatment with enteral nutrition. To improve compliance with the diet, the children received the formula through a nasogastric tube initially. After the first few days they were free to switch to drinking it, but almost all chose to stick with tube feeding.
Source: Terry A, Grogan JL, Casson DH, Dalzell AM, El-Matary W. Tube feeding therapy in paediatric Crohn's disease. Aliment Pharmacol Ther. 2011 Jul;34(2):260-1; author reply 261. doi: 10.1111/j.1365-2036.2011.04720.x.
Crohn's disease affects families, not just patients - December 15, 2012
Here's a surprising finding from a study of quality of life in families affected by chronic illness. Families that had a member with Crohn's disease reported lower quality of life than those that had a member with schizophrenia. Long waits to receive treatment, poor care by health professionals, and a heavy disease-related financial burden were the most prominent problems they faced.
Source: Loga S et al. Chronic illness and family: impact of schizophrenia and Crohn's disease on the family quality of life. Psychiatr Danub. 2012 Dec;24(4):359-66.
Naltrexone for Crohn's disease - November 29, 2012
I know many have been eagerly awaiting new studies of naltrexone, a medication used to treat drug and alcohol addiction that may have benefit in patients with Crohn's disease. Just released are the results of a pilot study in fourteen children with moderate-to-severe Crohn's. During an eight-week placebo-controlled phase, those in the naltrexone group achieved significantly decreased scores on an index of disease activity and 25 percent reached remission. (Presumably that means that two patients reached remission, if we assume that seven or eight children were randomized to naltrexone and remainder to the placebo.) I do not yet have access to the full text of the study, and will provide more details when I do.
But the abstract that provides the information above has a disturbing omission. Results are not given for the placebo group, inevitably raising the question of whether the patients who received the placebo did as well as, or almost as well as, those who received naltrexone. If they did, the improvements in the naltrexone group could have been due to a placebo effect, rather than the drug itself. I am eager to see the full text of the study and will report as soon as I am able to obtain it.
Source: Smith JP, Field D, Bingaman SI, Evans R, Mauger DT. Safety and tolerability of low-dose naltrexone therapy in children with moderate to severe Crohn's disease: a pilot study. J Clin Gastroenterol. 2012 Nov 21. [Epub ahead of print]
Figments of a disordered digestion - November 18, 2012
Perhaps indigestion is responsible for goblins and ghoulies! At least so Scrooge concludes in A Christmas Carol, by Charles Dickens (1843). Faced with Marley's ghost, he declares that a queasy stomach is deluding his senses. "A slight disorder of the stomach makes them cheats," he tells the ghost. "You may be an undigested bit of beef, a blob of mustard, a crumb of cheese, a fragment of underdone potato. There's more of gravy than of grave about you, whatever you are!" Holding up a toothpick, he insists: "I have but to swallow this, and be for the rest of my days persecuted by a legion of goblins, all of my own creation. Humbug, I tell you—humbug!"
"At this, the spirit raised a frightful cry, and shook its chain with such a dismal and appalling noise, that Scrooge held on tight to his chair, to save himself from falling into a swoon. But how much greater was his horror, when the phantom taking off the bandage around its head, as if it were too warm to wear indoors, its lower jaw dropped down upon its breast!"
Happy Thanksgiving everyone. Stay away from the specters of the stomach!
Psychosis as a symptom of Crohn's disease - October 27, 2012
A young woman entered a hospital suicidal and psychotic…and left with a diagnosis of Crohn's disease. The psychiatric symptoms resolved completely after surgery to remove two ileal obstructions. Crohn's disease can present in unlikely ways!
Source: Triantafillidis JK, Vagianos K, Rontos I. Psychotic reaction as a cardinal first clinical manifestation in a patient with Crohn's disease. J Crohns Colitis. 2012 Jul 30. [Epub ahead of print]
Maintaining remission with enteral nutrition - October 13, 2012
Did you know that enteral nutrition (EN) can be used as a maintenance treatment for Crohn's disease? In a recent study, twenty Crohnies used EN and a low-fat diet for five years after a resection (ileal or ileocolic). They were compared with twenty patients with Crohn's disease who followed an unrestricted diet after surgery.
Those who used EN were significantly less likely to need Remicaid (infliximab) to treat a recurrence than those eating whenever they chose (2/20 in the EN group vs. 9/20 in the control group; p = 0.03). Also, fewer patients in the EN group required surgery to treat a recurrence (1/20 vs. 5/20), although the difference did not reach statistical significance.
The patients in the EN group used about 1,200 calories of an elemental formula on a nightly basis, taken through a nasogastric tube, and ate around 600 calories of a low-fat diet by day (20 to 30 g of fat). It remains unclear whether the daytime diet needs to be low in fat to achieve these results; the benefits in the dietary therapy group could have been due to EN alone.
Source: Yamamoto T, Shiraki M, Nakahigashi M, Umegae S, Matsumoto K. Enteral nutrition to suppress postoperative Crohn's disease recurrence: a five-year prospective cohort study. Int J Colorectal Dis. 2012 Sep 27. [Epub ahead of print]
New options needed - September 30, 2012
I'd like to be able to report on a slew of new or soon-to-be-approved medications for Crohn's disease. However, the U.S. F.D.A. has not approved a single new drug to treat Crohn's disease since Cimzia (certolizumab pegol) in April 2008. The problem is not that potential meds have been rejected; it's that there haven't been any submitted for approval.
Drug development is a slow, slow process, but I'd love to see some new ideas out there. In the interim, we are left to make the most of the available therapies. In that regard, I've spotted a few recently published studies of enteral nutrition, one of which I will describe next week.
It's always good to be prepared - September 16, 2012
This is an FYI for those taking or considering Remicaid (infliximab). Persistent fever beginning two or three weeks after an infusion could be a medication side effect rather than a flare-up of Crohn's. There are two known cases: a patient who had 25 days of spiking fevers beginning nine days after a second infusion of Remicaid and one who had 13 days of high fevers starting three weeks after a second infusion. This is clearly an uncommon complication of the drug, but since the symptoms could be attributed to the underlying disease, it's good to be aware that another possibility exists.
Source: Katz J, Frank M. Prolonged fever after infliximab infusion. World J Gastrointest Pharmacol Ther. 2012 Jun 6;3(3):34-5.
A new light on drug-induced psoriasis - September 2, 2012
A study just published by French researchers may interest those taking biologic drugs for Crohn's disease. It has been clear for years that psoriasis can be a side effect of drugs such as Remicaid (infliximab) and Humira (adalimumab). But it can be hard to tell whether a patient with Crohn's or rheumatoid arthritis has developed psoriasis as a new-onset autoimmune disease or simply as a drug-induced side effect.
The investigators in this study found that drug-induced psoriasis had different characteristics than psoriasis appearing as an independent illness. When psoriasis showed up as a side effect of Remicaid or one of the other biologic drugs, in 33 to 43% of cases the lesions were pustular and occurred chiefly on the palms of the hands or the soles of the feet. Lesions of this type and distribution normally occur in fewer than 2% of psoriasis patients.
In patients who were being treated for psoriasis with a biologic and then developed drug-induced psoriasis as a side effect, the drug-induced lesions were of different types and appeared in different places than the patients' normal psoriasis sores.
If a patient tried a second or third biologic after developing drug-induced psoriasis and the skin condition recurred, the sores resembled (in type and location) those that appeared after the first biologic was used.
Source: Joyau C, Veyrac G, Dixneuf V, Jolliet P. Anti-tumour necrosis factor alpha therapy and increased risk of de novo psoriasis: is it really a paradoxical side effect? Clin Exp Rheumatol. 2012 Aug 31. [Epub ahead of print]
Iron up! - August 19, 2012
In a study of patients with IBD, 54% of those with iron-deficiency anemia did not receive any iron supplementation at all. Given that even mildly low iron levels can cause debilitating fatigue, treat anemia aggressively. Iron = energy!
Source: Ott C, Liebold A, Takses A, Strauch UG, Obermeier F. High prevalence but insufficient treatment of iron-deficiency anemia in patients with inflammatory bowel disease: results of a population-based cohort. Gastroenterol Res Pract. 2012;2012:595970. Epub 2012 Jul 30.
Sleep for a smooth-running tummy - August 12, 2012
Interrupted sleep can unsettle your belly, according to a survey of medical residents. The likelihood of irritable bowel syndrome increased with every hour of sleep deprivation while on call. Those with Crohn's disease don't need extra digestive turbulence, so turn off the computer and get to bed on time!
Source: Wells MM, Roth L, Chande N. Sleep disruption secondary to overnight call shifts is associated with irritable bowel syndrome in residents: a cross-sectional study. Am J Gastroenterol. 2012 Aug;107(8):1151-6.
The Golden Phoenix - July 21, 2012
Take a gander at this supremely elegant dessert, covered in 23-karat, edible gold leaf. It's called the Golden Phoenix, and it comes from Bloomsbury's, a bakery in Dubai. Gold salts once were used to treat rheumatoid arthritis, with the idea that they reduced inflammation. Ultimately studies showed they were ineffective; thus I doubt that the Golden Phoenix will do anything for Crohn's disease. But it is certainly a treat for the eyes!
Smoking → Crohn's disease? - July 15, 2012
Does smoking increase your risk for Crohn's disease? An unusually large study just examined that question. Among 229,111 women who participated, current smokers had almost double the risk of Crohn's disease as women who had never smoked. Former smokers had a slightly elevated risk of the disease, but giving up cigarettes decreased risk.
Source: Higuchi LM, Khalili H, Chan AT, Richter JM, Bousvaros A, Fuchs CS. A prospective study of cigarette smoking and the risk of inflammatory bowel disease in women. Am J Gastroenterol. 2012 Jul 10. doi: 10.1038/ajg.2012.196. [Epub ahead of print]
Regular runs - July 8, 2012
Ladies with Crohn's disease, you've already figured this one out…but now there's a study to confirm it. Women with Crohn's are approximately twice as likely as healthy women to suffer from diarrhea before and during their periods. Additionally, nearly half (46%) report worse IBD symptoms premenstrually.
Source: Bernstein MT, Graff LA, Targownik LE, et al. Gastrointestinal symptoms before and during menses in women with IBD. Aliment Pharmacol Ther. 2012 Jul;36(2):135-44. doi: 10.1111/j.1365-2036.2012.05155.x. Epub 2012 May 24.
Necessity is the mother of invention - June 24, 2012
Large family, short on loos? Faced with a similar dilemma, a gentleman of Belle Plaine, Minnesota, devised this two-story outhouse. He even put in a connector to the second floor of the main house, so you didn't have to go outside to do your business. In case you were wondering, the risk of unpleasantness for those using the first-floor facilities was eliminated by offsetting the three seats on the upper story. The remains fell behind a false wall on the lower level (unseen if perhaps not unheard!).
The buoyant belly - June 17, 2012
Are you making maximum use of your digestive tract? The nine-banded armadillo makes its gastrointestinal tract do double duty as a life jacket. When crossing a stream, it inflates its digestive tract for maximum buoyancy. How's that for a neat party trick?
Source: "Nine-banded armadillo," The Mammals of Texas - Online Edition, accessed June 16, 2012.
Long-term outcomes better with enteral nutrition than steroids - June 10, 2012
Here's a look at long-term outcomes among 31 children who received enteral nutrition (EN) as their initial treatment for Crohn's disease. During treatment, 84% reached remission. Over two years of follow-up, they had better growth and a lower risk of relapse than a comparison group of 26 youngsters treated with steroids.
This was a retrospective study, so the children weren't randomly assigned to the two treatments. Still, EN clearly benefited those who received it.
Source: Lambert B, Lemberg DA, Leach ST, Day AS. Longer-term outcomes of nutritional management of Crohn's disease in children. Dig Dis Sci. 2012 Jun 2. [Epub ahead of print]
Bellyache? Blame your belt - June 3, 2012
Heartburn? Nausea? Tummy in a twist? The author of a nineteenth-century medical textbook singles out the culprit: "Young men find it inconvenient to wear suspenders, and so wear a tight strap around their waist. This is a wretched habit….During meals the belt does not yield and the stomach, squeezed out of shape, cannot perform its normal functions; therefore this is a frequent cause of dyspepsia…." The cure: always wear suspenders!
Source: [George-Octave] Dujardin-Beaumetz, Diseases of the stomach and intestines: a manual of clinical therapeutics for the student and practitioner, trans. by E. P. Hurd (New York: William Wood & Company, 1886), 83.
An unwanted inheritance - May 13, 2012
A recent study suggests that familial Crohn's disease is more likely to be transmitted to a child if the mother rather than the father has Crohn's. Also, mothers are more likely to pass on Crohn's to daughters than to sons. In contrast, if the disease is handed down from a father, male and female children are equally likely to be affected.
It's a pity parents can't get rid of this unwanted gift rather than passing it on!
Source: Zelinkova Z, Stokkers PC, van der Linde K, Kuipers EJ, Peppelenbosch MP, van der Woude CP. Maternal imprinting and female predominance in familial Crohn's disease. J Crohns Colitis. 2012 Jan 23. [Epub ahead of print]
Throne improvements - May 6, 2012
Planning a bathroom renovation? Here are some creative (if pricey) toilets, including a gold-plated model (only 250,000 euros!) and a black-and-white number inspired by a spotted cow.
A little liverish? - April 29, 2012
Anyone out there with autoimmune liver disease? A study of primary sclerosing cholangitis (PSC) found that when this particular liver disease cropped up in patients with IBD, it occurred almost exclusively in those with colonic disease, with or without ileal involvement. Among 78 PSC patients with Crohn's disease, 53 had colitis, and 17 had ileocolitis. Just four had ileitis alone, and in four the disease location was unknown.
Source: Boonstra K, van Erpecum KJ, van Nieuwkerk KM, et al. Primary sclerosing cholangitis is associated with a distinct phenotype of inflammatory bowel disease. Inflamm Bowel Dis. 2012 Mar 8. doi: 10.1002/ibd.22938. [Epub ahead of print]
Adding in allopurinol - April 22, 2012
When 6-MP or azathioprine can't calm Crohn's disease alone, some doctors have started to add allopurinol to the mix (see my blog posts of February 20 and 27, 2012). In the most recent report, doctors reviewed the cases of 110 patients with ulcerative colitis or Crohn's disease who tried this tactic. It's interesting to look at the results in some of the subgroups.
Among 25 patients who started the drug combination because of abnormal liver function on 6-MP or azathioprine, 20 achieved normal liver function on the combo. Also, 24 of 28 patients who had other drug side effects on 6-MP or azathioprine (rashes, arthralgias, nausea, fatigue, etc.) were able to tolerate treatment once allopurinol was added to the mix.
Ten of 17 patients who weren't able to achieve full remission on 6-MP or azathioprine went into remission on the combination therapy, and 14 of 23 steroid-dependent patients were able to discontinue corticosteroids.
This was a retrospective study, rather than a trial in which patients were randomly assigned to 6-MP or azathioprine plus allopurinol or a placebo. But, as the authors conclude, the results are promising enough to justify performing a randomized, controlled trial.
There aren't that many treatment options for Crohn's disease. If allopurinol can make the standard immunosuppressive drugs more effective or tolerable for people who can't otherwise benefit from them, it will be an excellent addition to the medical armorarium.
Source: Smith MA, Blaker P, Marinaki AM, Anderson SH, Irving PM, Sanderson JD. Optimising outcome on thiopurines in inflammatory bowel disease by co-prescription of allopurinol. J Crohn's Colitis. 2012 Mar 2. doi: 10.1016/j.crohns.2012.02.007 [Epub ahead of print]
Rifaximin for Crohn's disease - April 15, 2012
Antibiotics such as sulfasalazine and metronidazole (Flagyl) have been used to treat Crohn's disease for decades. More recently, some doctors have been prescribing a newer antibiotic called rifaximin. In a study of an extended-release version of rifaximin, 61% of patients who received an 800-mg, twice-daily dose for 12 weeks achieved remission, compared with 43% of patients who received a placebo, a statistically significant difference. After the treatment ended, patients who had received rifaximin were significantly more likely to remain in remission for an additional 12 weeks than those in the placebo group (45% vs. 29%).
The formulation of rifaximin used in this study was designed to target the intestines, with release of the drug not beginning until the tablets reach the small intestine. Most of the patients didn't receive the antibiotic as their only therapy. People taking biologic drugs or recently receiving steroids were excluded from the study, but the majority of participants were on other stable maintenance therapies that they continued over the course of the trial. They had moderately active Crohn's disease at the beginning of treatment, in spite of their maintenance medications.
A puzzling aspect of this study was that two other groups of patients, receiving 400 mg or 1200 mg of rifaximin twice daily, did not achieve significantly better results than the patients who received the placebo. Typically one would expect a dose-response relationship—that is, higher remission rates with a higher dose. Therefore, further trials will be necessary to clarify whether rifaximin is truly effective in inducing remission. Because it is considerably more expensive than older, generic medications such as sulfasalazine, it would be ideal to have a study directly comparing sulfasalazine, rifaximin, and placebo to determine whether or not the newer antibiotic offers a clear advantage.
Source: Prantera C, Lochs H, Grimaldi M, et al. Rifaximin-extended intestinal release induces remission in patients with moderately active Crohn's disease. Gastroenterology. 2012 Mar;142(3):473-481.e4. Epub 2011 Dec 6.
Time for a little humor - April 1, 2012
Crohn's disease is no joke, but occasionally its sufferers need a little comic relief. Enjoy this list of bloopers supposedly written by doctors on patient charts. Don't miss the unusual discovery made during a rectal exam, nor the patient who found an alternative to a bowel resection.
Cutting the cord - March 25, 2012
According to a recent survey, many young adults with IBD are surprisingly dependent on their parents to help them manage the disease. Among respondents aged 19 to 21, only 35% actively participated in scheduling their appointments, only 40% took the lead in remembering appointments, and only 30% took the primary responsibility for contacting their doctor when problems arose between visits.
If you have a teen with IBD, it's worth considering whether you should start handing over more of the disease-management responsibilities. It may be particularly important to set such expectations for young men. In this study, they were significantly less likely than their female peers to order medication refills or prepare questions for the doctor.
Source: van Groningen J, Ziniel S, Arnold J, Fishman LN. When independent healthcare behaviors develop in adolescents with inflammatory bowel disease. Inflamm Bowel Dis. 2012 Feb 28. doi: 10.1002/ibd.22937. [Epub ahead of print]
Too clean for our own good? - March 18, 2012
Is Crohn's disease more common today because kids aren't exposed to enough dirt and germs? Supporters of this "hygiene hypothesis" speculate that our squeaky-clean homes and fondness for soap and water are robbing our children of healthy immune systems built through contact with microbes.
However, a good-sized study (including 527 patients with ulcerative colitis, 468 with Crohn's disease, and 562 controls) found no support for this theory. IBD patients and controls did not differ significantly in their childhood exposure to microbes, as measured by factors such as the number of parasitic infections experienced, the amount of antibiotics used, family size, exposure to animals, receipt of vaccinations, or an urban upbringing. The only significant risk factors for Crohn's disease were the old faithfuls: a family history of IBD, a history of appendectomy, and cigarette smoking.
Source: Castiglione F, Diaferia M, Morace F, et al. Risk factors for inflammatory bowel diseases according to the "hygiene hypothesis": a case-control, multi-centre, prospective study in Southern Italy. J Crohns Colitis. 2012 Apr;6(3):324-9. Epub 2011 Oct 7.
The few and the brave - March 9, 2012
When it comes to autoimmune diseases, Crohnies are among the select. In a study conducted in Sardinia, Italy, the prevalence of Crohn's disease was only 15 cases per 100,000 people, compared with 464 for type 1 diabetes, 552 for rheumatoid arthritis, 939 for psoriasis/psoriatic arthritis, and 2,619 for autoimmune thyroiditis. The prevalence of our sister inflammatory bowel disease, ulcerative colitis, was 124 per 100,000. Of 12 autoimmune diseases assessed, Crohn's disease was the least common.
Source: Sardu C, Cocco E, Mereu A, et al. Population-based study of 12 autoimmune diseases in Sardinia, Italy: prevalence and comorbidity. PLoS One. 2012;7(3):e32487. Epub 2012 Mar 2.
Instead of steroids - February 19, 2012
A working group from the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition has taken a careful look at the medical literature on enteral nutrition, and concluded that (insert three drum rolls and a trumpet flourish here!) it is an effective alternative to steroids for children with Crohn's disease. The group recommends enteral nutrition as a first-line therapy for inducing remission "regardless of active disease location." Those searching for an alternative to steroids, take note!
Source: Critch J, Day AS, Otley A, King-Moore C, Teitelbaum JE, Shashidhar H; on behalf of the NASPGHAN IBD Committee. Use of enteral nutrition for the control of intestinal inflammation in pediatric Crohn disease. J Pediatr Gastroenterol Nutr. 2012 Feb;54(2):298-305.
The self-cleaning colon - February 12, 2012
Colons are like modern ovens and freezers: they clean themselves. But the widespread, if misguided, notion that colons need cleansing has hung around for centuries. Nineteenth- and twentieth-century ads for laxatives trumpeted the risks of "autointoxication": the supposed poisoning of the body due to the presence of undigested food. One advertiser warned dramatically, "When the bowels stop working they become filled with putrid, rotting matter, forming poisonous gases that go through the whole body."
In response to such nonsense, Arthur Hurst wrote sadly in 1935, "The colon is slandered every day in the advertising columns of the popular press, which accuse it of sins it never commits, and the mass suggestion which results from constantly reading about the disastrous effects of intestinal intoxication results in most of the lay public and many of the medical profession joining in these slanders. By promoting the sale of purgatives and encouraging the use of various other methods of irritating the colon, these slanders result in maltreatment. No wonder that the colon is unhappy." Sadly, the same slanders against the noble colon proliferate on the Internet today.
Source: James C. Whorton, Inner hygiene: constipation and the pursuit of health in modern society (New York: Oxford University Press, 2000), 81, 89.
Regaining response to Remicaid - February 5, 2012
If you are losing response to Remicaid, should you ask for an increased dose or more frequent infusions? In a retrospective study of 168 patients with Crohn's disease, decreasing the interval between infusions (from eight to four weeks) was compared with doubling the medication dose (from 5 to 10 mg/kg). There was no statistically significant difference between the two methods in early or sustained clinical response. However, doubling the number of infusions is inconvenient for patients and costly in staff time and equipment. Thus the authors conclude that doubling the dose may be the better choice.
Source: Katz L, Gisbert JP, Manoogian B, ed al. Doubling the infliximab dose versus halving the infusion intervals in Crohn's disease patients with loss of response. Inflamm Bowel Dis. 2012 Jan 31. doi: 10.1002/ibd.22902. [Epub ahead of print]
What's in a name? - January 29, 2012
Crohn's, crones, chron's, chrones, crohnes…Crohn's disease must be the most frequently misspelled condition in the world. It's capitalized because it comes from a proper name, that of Dr. Burrill B. Crohn, who was the lead author of a 1932 article that helped to define the disease. However, it might equally have been called Dalzeil's disease (equally challenging to spell and even more to pronounce!). The Scottish surgeon T. Kennedy Dalzeil (pronounced "dee-yell") was the first to recognize what we today call Crohn's disease as a separate clinical entity. In describing the disease at a meeting of the British Medical Association in 1913, he said graphically, "the affected bowel gives the consistence and smoothness of an eel in a state of rigor mortis…."
Source: Kyle J. Dalzeil's disease—66 years on. BMJ. 1979 31 Mar;1:876-77.
Increase your happiness quotient - January 22, 2012
Down in the dumps due to Crohn's disease? Here's a way to brighten your day. In a 2011 study, mood improved in depressed people when they visualized themselves engaged in a happy or positive activity. They had to picture themselves participating in the activity, rather than creating a mental image of others happily engaged. Envisioning themselves engaged in emotionally neutral activities had no effect on mood.
Study participants (students) were given picture/word combinations as cues to help them generate positive images. For example, a scene of students in a classroom was paired with the word "understanding." You, too, can prepare pictures and words in advance to help you summon up happy images at grim moments.
Source : Pictet, A, Coughtrey, AE, Mathews, A, Holmes, EA. Fishing for happiness: The effects of generating positive imagery on mood and behaviour. Behav Res Ther. 2011 December; 49(12): 885-891.
The first corticosteroid - January 15, 2012
If you've ever taken a steroid to treat a flare of Crohn's disease, give a nod of thanks to chemist Lew Sarrett. In 1944 he pioneered a 42-step process to synthesize cortisone—the first corticosteroid—from ox bile. But…the process produced such a tiny amount of cortisone that 14,600 cows would have to be slaughtered to treat a single patient for a year. Per ounce, cortisone was over 100 times pricier than gold.
Given the demand for the wonder drug, within a few years cheaper methods were developed to synthesize it from steroids found in soybeans and yams.
Source: B. Werth, The billion-dollar molecule: one company's quest for the perfect drug (New York: Simon and Schuster, 1994): 128-29.
It could always be worse - January 8, 2012
Even if modern medicine hasn't cured Crohn's disease yet, we are at least free from many minor irritants of the past. In an 1845 letter at the Pierpont-Morgan Library, Charles Dickens laments a lively colony of fleas that infested him during a trip to Italy. They "sowed themselves, like self-acting mustard and cress, in my flannel dressing-gown," Dickens reported. "I find myself perpetually stopping in public places to scratch myself, like a Dog. And…when I listen very hard outside my Portmanteau, I think I can distinctly hear them, leaping up inside the lid, and knocking their heads against it." Ugh!
A New Year's gift for patients with Crohn's disease? - January 1, 2012
How many days have you waited to receive test results from a doctor? How often have you been given a quick overview of the findings—but not the full details you really wanted to know? A welcome change may be at hand. Back in September, the U.S. Department of Health and Human Services, joined by several other Federal agencies, proposed that patients be permitted to receive their test results directly from laboratories.
The fate of the proposed rule is not yet known, but the comment period closed in mid-November. Here's hoping a positive decision will be handed down soon.
Sharing your strength - December 25, 2011
How do you encourage a child with Crohn's disease to push on in the face of sickness and pain? Dr. Henry Cloud tells of a moment in his childhood when his mother reached out and gave him the strength to go on. He'd been hospitalized for over a month, not with Crohn's but with complications of mononucleosis. He was so exhausted and impossibly behind in his schoolwork that one morning he froze half-dressed and couldn't bear to go on. When his mother came to check on him, he told her he couldn't do it anymore. She gave him a hug and then said something he never forgot:
"'I know. Sometimes I don't want to go to work either, when I feel that way.'
The world kind of stopped for a moment. 'What?' I asked. 'You feel like you don't want to go to work sometimes?'
'Sure. Sometimes when I'm sick or don't feel well, it just is too much, and I don't want to go either.'
'But you do…'
She just nodded.
All I know," Cloud concludes, "is at that point, something had shifted inside. I was still as tired, overwhelmed, and sick as I had been when I was frozen. But, for some reason, suddenly I felt as if I could do it."
Cloud's mother didn't reinforce his exhaustion and despair, but nor did she discount them. Instead, she connected them to his ability to persevere. As Cloud writes, "she was both feeling bad and went….Our character and abilities grow through internalizing from others what we do not possess in ourselves."
Source: Henry Cloud, Integrity: the courage to meet the demands of reality (New York: Harper, 2006): 88-90.
The forgotten treatment for Crohn's disease - December 18, 2011
What if you could actually treat Crohn's disease with diet? What if there were dozens of published studies of the diet in the medical literature? What if new studies were appearing each year?
Well, there is such a diet for treating Crohn's disease, and it is called enteral nutrition. As stated in the most recent review of this therapy, "there should now be little doubt that [enteral] nutrition regimens have the potential to induce remission in inflammatory exacerbations of Crohn's disease. A clinically defined remission rate of well over 50% is to be expected." For those looking for maintain rather than induce remission, the authors add, "enteral nutrition supplementation can now be reasonably considered an alternative or an adjunct to drug therapy in Crohn's disease." Why not give it a try?
Sources: Alastair F, Emma G, Emma P. Nutrition in inflammatory bowel disease. JPEN J Parenter Enteral Nutr. 2011 Sep;35(5):571-80. Epub 2011 Aug 8.
Don't vacillate, vaccinate! - December 11, 2011
If you are planning to start an immunosuppressive drug, make sure to get your vaccinations first. Among IBDers who received the hepatitis B vaccine, only 53% had an effective immune response. The worst results were seen in patients taking immunosuppressive drugs and those with active disease. Similarly, in an earlier study, pneumococcal vaccination was less effective in patients with Crohn's disease or ulcerative colitis who were taking Remicaid or Remicaid plus azathioprine.
Sources: Altunöz ME, Senates E, Yesil A, et al. Patients with inflammatory bowel disease have a lower response rate to HBV vaccination compared to controls. Dig Dis Sci. 2011 Dec 7. [Epub ahead of print]. Fiorino G, Peyrin-Biroulet L, Naccarato P, et al. Effects of immunosuppression on immune response to pneumococcal vaccine in inflammatory bowel disease: A prospective study. Inflamm Bowel Dis. 2011 Jun 14. doi: 10.1002/ibd.21800. [Epub ahead of print]
A window into the stomach - December 4, 2011
The stomach could star in a murder mystery. The digestive juices breaking down your latest meal are made up of fiercely corrosive hydrochloric acid, with a few digestive enzymes mixed in. Without the layer of protective mucus coating the stomach lining, our own gastric juice might eat us up.
It wasn't until the nineteenth century that the caustic chemistry of digestion was understood. An army surgeon, Dr. William Beaumont, made the discovery thanks to a patient with a shotgun wound. When the wound healed, patient Alexis St. Martin was left with a gastrocutaneous fistula: an opening from the outer surface of the tummy straight into his stomach. Dr. Beaumont took advantage of this conveniently placed fistula to insert a bit of meat attached to a string. On removing the sample, he could see it had been broken down chemically, and he was able to retrieve stomach fluids for analysis.
Unfortunately, neither doctor nor patient reaped the fame they deserved from the pioneering discovery. However, for those who want to know more, they are the protagonists of a newly published historical novel, Open Wound: The Tragic Obsession of Dr. William Beaumont, by Jason Karlawish (University of Michigan Press, 2011).
Source: Abigail Zuger. "Doctor and patient, bound by mutual dependency." NY Times: D5, 29 Nov 2011.
Animated immunology - November 20, 2011
Want to learn more about how the immune system works? Enjoy this cute, animated introduction to antibodies, complement proteins, T lymphocytes, and other immunological arcana. Don't miss clicking on the "read more" bubble at the bottom of each page to get the full scoop. For example, you'll discover that "immunity" in Roman times meant protection from taxes rather than protection from disease!
All about iron - November 13, 2011
Weary, wan, pale, and weak? You might be anemic. But which are better: iron infusions or iron tablets?
The authors of a recent review conclude that they are equally effective in people with IBD. Iron taken orally works just as quickly as the intravenous variety. Needle-phobic folks, rejoice!
Rizvi S, Schoen RE. Supplementation with oral vs. intravenous iron for anemia with IBD or gastrointestinal bleeding: is oral iron getting a bad rap? Am J Gastroenterol. 2011 Nov;106(11):1872-9. doi: 10.1038/ajg.2011.232.
Variations on a theme - November 6, 2011
Don't miss these amazing variations on the humble toilet from the collection of a museum in Austria. There are even two supported by sphinxes and a couple of others designed to imitate a stack of books. Our 21st-century toilets seem very pedestrian in comparison.
Intestinal elasticity! - October 30, 2011
Is your intestinal tissue lithe and limber? It turns out that rectal tissue in people with Crohn's disease may be thicker and more rigid than in healthy folks, even in the absence of active disease. Patients with ulcerative colitis also have thicker rectal tissue, but only during a flare. In addition, they don't have the same loss of elasticity as people with Crohn's.
These findings come from a small study using a new technology called endoscopic ultrasound elastography, which can be used to measure tissue stiffness by ultrasound. The results of the study, although still very tentative, suggest that such measurements may be useful in the future in distinguishing between Crohn's colitis and ulcerative colitis.
Source: Rustemovic N, Cukovic-Cavka S, Brinar M, et al. A pilot study of transrectal endoscopic ultrasound elastography in inflammatory bowel disease. BMC Gastroenterol. 2011 Oct 20;11(1):113. [Epub ahead of print]
Aloe: balm or burden? - October 23, 2011
Taken internally, aloe is best known as a laxative. Yet it is sometimes promoted as an alternative treatment for digestive diseases.
In a randomized, placebo-controlled, cross-over trial, it was recently tested in people with irritable bowel syndrome (IBS). A substantial number of patients dropped out before completing the trial. Withdrawing due to increased symptoms was more common when taking the aloe. Among those who finished the study, aloe had no more effect on disease-specific or overall quality of life than the placebo.
What if you have Crohn's disease rather than IBS? Well, no one knows what the results would be since there haven't been any published studies of the plant in patients with Crohn's. But given aloe's ability to act as a gastrointestinal irritant, I would steer clear.
Source: Hutchings HA, Wareham K, Baxter JN, et al. A randomised, cross-over, placebo-controlled study of Aloe vera in patients with irritable bowel syndrome: effects on patient quality of life. ISRN Gastroenterol. 2011;2011:206103. Epub 2010 Oct 11.
Home improvements - October 17, 2011
For the Crohn's patient who has everything, how about a temporary tattoo for the toilet seat? From a "Single Rose" to a "Moose at Sunset," now you can choose among dozens of wipe-clean, reusable, toilet-lid appliques! See the selection here.
Have a stricture? Get a picture! - October 9, 2011
There are two types of strictures in Crohn's disease: inflammatory and fibrotic. The first can disappear with anti-inflammatory treatments, including steroids, biologics, and enteral nutrition. The second must be sliced open, stretched, or sliced out. The problem is figuring out which one you have.
In a newly published study, doctors found that MRI enterography (an MRI using contrast material to create images of the small intestine) was highly accurate at distinguishing between the two types of strictures. In the only case where they fumbled a diagnosis, mistaking a fibrotic for an inflammatory stricture, there was a layer of mild inflammation on top but fibrosis lurking beneath. This form of imaging may have the potential to help patients and doctors make better treatment decisions.
Source: Fornasa F, Benassuti C, Benazzato L. Role of magnetic resonance enterography in differentiating between fibrotic and active inflammatory small bowel stenosis in patients with Crohn's disease. J Clin Imaging Sci. 2011;1:35. Epub 2011 Jun 25.
The PeePoo bag...because everyone has to go - October 2, 2011
Everyone has to go, but a staggering 40% of the residents of this planet don't have access to a toilet. Enter the PeePoo, a snazzy, single-use, personal-sanitation solution. It's a biodegradable plastic bag with a gauze lining containing urea. Do your business into the bag, knot the top closed, and bury it. The plastic breaks down into harmless organic compounds; the urea kills bacteria, viruses and parasites in urine and feces, in the process converting itself into fertilizer that will be appreciated by nearby plants.
Learn more: http://www.peepoople.com/showpage.php?page=3_8.
Enteral nutrition vs. Crohn's disease: enteral nutrition wins! - September 25, 2011
Among 106 children treated with enteral nutrition for eight weeks, 86 reached remission! Some children drank the formula by mouth and others received it through a tube, but the remission rates were not statistically different (75% and 85%, respectively). Lesson learned: as long as the formula reaches your guts, it doesn't matter how it gets there.
Source: Rubio A, Pigneur B, Garnier-Lengliné H, et al. The efficacy of exclusive nutritional therapy in paediatric Crohn's disease, comparing fractionated oral vs. continuous enteral feeding. Aliment Pharmacol Ther. 2011 Jun;33(12):1332-9. doi: 10.1111/j.1365-2036.2011.04662.x. Epub 2011 Apr 20.
Fat in the wrong places? - September 16, 2011
Skinny everywhere except your legs and belly? You might be low on albumin, whether as a result of malabsorption or unsuspected liver disease. Fluid can leak from the blood into the lower limbs and abdomen when albumin is in short supply. The puffed-up look is from fluids, not fat.
Source: www.everydayhealth.com/digestive-health/experts-digestive-health-conditions-and-losing-weight.aspx.
A thumbs down for prebiotics - September 11, 2011
Crohn's disease bites the bank account, not just the body, so we don't want to waste money on worthless treatments. It's looking more and more as if prebiotics fall into that category. In a randomized, double-blind trial, a prebiotic was no more effective than a placebo in reducing symptoms and inflammation in patients with moderately active Crohn's. In addition, those randomized to the prebiotic were significantly more likely to report abdominal pain, flatulence, and a rumbling tummy than those who received the placebo.
Source: Benjamin JL, Hedin CR, Koutsoumpas A, et al. Randomised, double-blind, placebo-controlled trial of fructo-oligosaccharides in active Crohn's disease. Gut. 2011 Jul;60(7):923-9. Epub 2011 Jan 24.
Stool studies - September 6, 2011
Who'd have thunk it? There's actually an academic specialty devoted to the study of feces: coprolithology (kopros, feces + lithos, stone). Coprolithologists cut fossilized droppings ("coprolites") into onion-skinlike slices to investigate the eating patterns of prehistoric animals.
Given our affection for indoor plumbing, I fear that future archaeologists will find few human coprolites to analyze.
Source: M. Novacek, Time Traveler: In Search of Dinosaurs and Ancient Mammals from Montana to Mongolia (New York: Farrar, Straus and Giroux, 2002): 67.
Avoiding infusion reactions with Remicaid - August 27, 2011
What's the best way to avoid infusion reactions from Remicaid (infliximab)? In a study of more than 2,000 infusions in 415 patients, premedicating with a corticosteroid did not affect the rate of infusion reactions. However, using concurrent azathioprine, 6-MP, or methotrexate significantly reduced the rate of reactions in patients with IBD.
In another finding from this study, infusion reactions were no more common after a one-hour than a two-hour infusion. But patients weren't allowed to have the speedier infusions unless their last three two-hour infusions had been troublefree, so those who received the shorter infusions may have been less prone to reactions in general. Still, the finding suggests that patients who tolerate their infusions well may be able to handle and benefit from a shorter infusion time.
Source: Lee TW, Singh R, Fedorak RN. A one-hour infusion of infliximab during maintenance therapy is safe and well tolerated: a prospective cohort study. Aliment Pharmacol Ther. 2011 Jul;34(2):181-7. doi: 10.1111/j.1365-2036.2011.04699.x. Epub 2011 May 25.
Swedes use enteral nutrition to treat kids with Crohn's - August 21, 2011
In a survey of Swedish medical centers treating children with IBD, 96% of respondents indicated that their units use enteral nutrition as a primary and/or maintenance therapy for Crohn's disease. (Units covering almost 90% of Sweden's pediatric population answered the survey.) I continue to find it baffling that this safe and effective therapy is so well accepted in Europe and yet so little used in the U.S.
Source: Gråfors JM, Casswall TH. Exclusive enteral nutrition in the treatment of children with Crohn's disease in Sweden: a questionnaire survey. Acta Paediatr. 2011 Jul;100(7):1018-22. doi: 10.1111/j.1651-2227.2011.02178.x. Epub 2011 Feb 22.
Fistula, be gone! A new approach to treating a pesky problem - August 14, 2011
Here's a unique approach to treating fistulas in Crohn's disease. Mesenchymal stem cells from the bone marrow were harvested from patients burdened with complex or multiple fistulas. Then each patient received injections of his or her own stem cells directly into the fistulas. Patients received from two to five injections, spaced at four-week intervals.
Of 10 people who received the injections, seven had complete fistula closure; the remaining three showed improvement. It took only two injections for most patients to be in remission as assessed by the Crohn's Disease Activity Index. Adding to the good news, none of the fistulas started to drain again during 12 months of follow-up.
Source: Ciccocioppo R, Bernardo ME, Sgarella A, et al. Autologous bone marrow-derived mesenchymal stromal cells in the treatment of fistulising Crohn's disease. Gut. 2011 Jun;60(6):788-98. Epub 2011Jan 21.
Stem-cell transplantation in Crohn's disease - August 7, 2011
Stem-cell transplantation (SCT) for Crohn's disease? Here's the latest report on patients treated with autologous hematopoietic SCT (autologous means that their own stem cells, rather than those of the donor, were harvested and reinjected).
One patient did rather well. He had a five-year remission—although 6-MP and Remicaid, both started six months after the procedure, may have played a role in maintaining the improvement.
Another patient achieved a partial remission. Helped by medication (first azathioprine and later Cimzia) he remained in relatively good shape six years later, with occasional vomiting after meals.
A third patient had the stem cells harvested but didn't have the transplant because the harvesting process put her in remission. She relapsed two years later.
Overall, this looks like one more way to fight back against Crohn's disease for patients who are out of options. But it's clearly not a cure, nor even a surefire way to become medication-free. Next week I'll write about a different way of using stem cells, a technique with a more modest goal but promising results.
Source: Hommes DW, Duijvestein M, Zelinkova Z, et al. Long-term follow-up of autologous hematopoietic stem cell transplantation for severe refractory Crohn's disease. 10 June 2011. doi: 10.1016/j.crohns.2011.05.004 (article in press).
Using psychology to fight fatigue - July 31, 2011
Use psychology to fight fatigue caused by Crohn's disease? Maybe. In a small pilot study, researchers tested two psychological problem-solving tools in Crohn's patients burdened by fatigue. One method, "problem-solving therapy," involves breaking down each problem into smaller steps: first defining the problem and setting a goal, then brainstorming solutions, weighing the pros and cons of each, choosing one and trying it, and evaluating if it was effective. The other method, "solution-focused therapy," begins with the assumption that no problem exists all the time. To solve the problem, you identify the moments when the problem isn't present and do more of what you were doing in those troublefree moments.
Fatigue decreased in patients assigned to each of the techniques, especially solution-focused therapy, although the small size of the study precluded drawing any firm conclusions. Regardless, I plan to add both methods to my problem-solving armamentarium. They could be applied to plenty of dilemmas besides exhaustion.
Source: Vogelaar L, van't Spijker A, Vogelaar T, et al. Solution focused therapy: A promising new tool in the management of fatigue in Crohn's disease patients: Psychological interventions for the management of fatigue in Crohn's disease. J Crohn's Colitis. 11 July 2011. doi: 10.1016/j.crohns.2011.06.001 (article in press).
A real pain in the butt - July 24, 2011
Australian doctors asked patients with perianal Crohn's disease whether the symptoms had ever made them feel life wasn't worth living (one-third said yes) or suicidal (13% said yes). Although the 69 patients who chose to respond to the survey (out of 130 who received it) might have been those most seriously affected, the results are a testimony to how thoroughly unpleasant perianal disease can be.
Source: Mahadev S, Young JM, Selby W, Solomon MJ. Self-reported depressive symptoms and suicidal feelings in perianal Crohn's disease. Colorectal Dis. 2011 Mar 17. doi: 10.1111/j.1463-1318.2011.02613.x. [Epub ahead of print]
Enteral nutrition for perianal Crohn's disease - July 24, 2011
There's no easy answer when it comes to treating perianal Crohn's disease, although Flagyl (metronidazole) can be a big help. For those still frustrated after trying the usual options, enteral nutrition is yet another possibility. The latest report describes the cases of three children. Enteral nutrition was used as the sole treatment to heal the site and induce remission after inserting a seton (in one child), and after draining an abscess and laying open a fistula (in another child). The third child required a combination of surgical drainage, metronidazole, enteral nutrition, and azathioprine, but none of the children had to use steroids or a biologic drug.
Source: Wong S, Lemberg DA, Day AS. Exclusive enteral nutrition in the management of perianal Crohn's disease in children. J Dig Dis. 2010 Jun;11(3):185-8.
Methotrexate = nausea? A possible solution - July 17, 2011
Does methotrexate make you nauseated? Ondansetron—a drug used to treat nausea in cancer patients—might help. In a study of children with Crohn's disease, nausea occurred in only one of 50 patients pretreated with ondansetron before each week's injection of methotrexate. In contrast, six of 10 children who were not pretreated experienced nausea within their first three months on methotrexate.
Luckily, the ondansetron is taken orally, so pretreatment doesn't mean an additional injection. One caution: this was a retrospective study, so it would be helpful to have the results confirmed in a randomized, placebo-controlled trial.
Source: Kempinska A, Benchimol EI, Mack A, Barkey J, Boland M, Mack DR. Short-course ondansetron for the prevention of methotrexate-induced nausea in children with Crohn's disease. J Pediatr Gastroenterol Nutr. 2011 Jun 14. [Epub ahead of print]
Beauty in strange places - July 10, 2011
I vote the Newtown Creek Wastewater Treatment Plant the most beautiful sewage-treatment plant in the world. The attached photo (click on it to enlarge) shows the plant's "digester eggs" at night. From the walkway above each egg, you can peer down through a porthole at the bubbling black soup inside.
The teeming stew is composed of billions of bacteria doing their job of processing organic wastes. The eggs function like giant versions of the human colon: the bacteria inside act like the gut microbes that turn the remains of our meals into stool. Click here to view additional, striking images of the digester eggs.
Gratitude for small things - July 3, 2011
Eager for new treatments for Crohn's disease? Spare a moment's gratitude for the humble nematode, which can help researchers study intestinal inflammation. The intestinal wall of this one-millimeter-long worm is only 20 cells thick, and transparent (like the rest of the tiny creature), so its workings can be easily studied.
By feeding the nematode one bacterial species at a time, scientists can examine the interaction between intestinal cells (enterocytes) and a given bacteria. It's a lot easier than analyzing similar interactions in unwieldy, omnivorous humans. All hail the conqueror worm! (with apologies to Edgar Allan Poe).
Source: Lin J, Hackam DJ. Worms, flies and four-legged friends: the applicability of biological models to the understanding of intestinal inflammatory diseases. Dis Model Mech. 2011 Jul-Aug;4(4):447-56. Epub 2011 Jun 13.
Disappointing results for Cimzia in Crohn's disease - June 26, 2011
Sadly, the results of the latest study of Cimzia are unimpressive. The remission rate after six weeks of treatment was only 32%, not significantly different from the remission rate in the placebo group. The study included 439 patients with moderate-to-severe Crohn's disease who had not previously taken any of the biologic drugs.
Source: Sandborn WJ, Schreiber S, Feagan BG, et al. Certolizumab pegol for active Crohn's disease: a placebo-controlled, randomized trial. Clin Gastroenterol Hepatol. 2011 May 13. [Epub ahead of print]
Animal magnetism - June 19, 2011
Nails, barbed wire, grass—it's all the same to a grazing cow. The solution: a cow magnet! About 3 inches long, it settles in the second of a cow's four stomach chambers and remains there for life. Bits of ingested metal stick to the magnet rather than embed painfully in the stomach lining.
Clearly, preventive medicine comes in many forms—but don't try this one for Crohn's disease!
Humira for Crohn's disease = no more steroids? - June 12, 2011
Getting off steroids is often the rationale for starting a biologic drug. But in a recent study, only 26% of patients who were taking steroids when they began Humira were in steroid-free remission after using the biologic for a year. After three years of Humira, 23% were in remission without steroids.
I guess we're still awaiting a miracle drug. In the meantime, don't forget enteral nutrition, which can substitute for steroids in inducing remission.
Source: Kamm MA, Hanauer SB, Panaccione R, et al. Adalimumab sustains steroid-free remission after 3 years of therapy for Crohn's disease. Aliment Pharmacol Ther. 2011 Jun 5. doi: 10.1111/j.1365-2036.2011.04717.x. [Epub ahead of print]
Brain food - June 12, 2011
When you prepare your next meal, consider this: Without cooking, which makes food easier to digest, we might still be like apes, browsing for hours on fruit and foliage to get enough calories to survive. Indeed, cooking may have helped us evolve clever brains by supplying the energy guzzled by our bumper crop of neurons. The brain makes up only 2% of our body mass, but consumes 20% of the energy we need to function.
Source: Herculano-Houzel S. Scaling of brain metabolism with a fixed energy budget per neuron: implications for neuronal activity, plasticity and evolution. PLoS One. 2011 Mar 1;6(3):e17514.
Superheroes? No, supraorganisms - June 5, 2011
We're not just human beings, we are supraorganisms, made up of interacting human components and microbes! Some microbes visit a body part and move on; others are permanent residents of an ecosystem, whether in the mouth, nose, gut, or other region. Indeed, our bacteria immigrate and emigrate: among "body sites, between cohabiting individuals, and between ourselves and the myriad of environments we contact on a daily basis."
Increasingly it appears that a different range of bacteria inhabits different body sites (mouth vs. gut, for example). Within each site, many bacteria are transients that "appear in a body habitat and disappear soon after." A much smaller group of bacteria form an individual's "core microbiome," bacteria that show up consistently when a given body habitat is sampled. We begin developing our own, unique core microbiomes at birth.
Source: Caporaso JG, Lauber CL, Costello EK, et al. Moving pictures of the human microbiome. Genome Biol. 2011 May 30;12(5):R50. [Epub ahead of print]
An old treatments for Crohn's disease gets another look - May 29, 2011
I just read about an old treatment for Crohn's disease that's new to me. Patients suffering a severe flare of IBD were injected intravenously with one of a variety of different vaccines (among them, typhoid vaccine and anti-dysentery serum) with the aim of causing a high fever. It was hoped that the immune system, provoked into fighting the fever, would also control the flair of IBD.
Success was spotty: sometimes it worked surprisingly well, prompting dramatic remissions, and sometimes it didn't work at all. Reviewing this history, the authors of a recent case report suggest developing IBD therapies to activate our innate immunological response to fever in an "attempt to reassert immune system control over pathogens or harmful indigenous flora." Interesting concept, although I suspect easier said than done.
Hoption Cann SA, van Netten JP. Spontaneous remission of Crohn's disease following a febrile infection: case report and literature review. BMC Gastroenterol. 2011 May 19;11(1):57. [Epub ahead of print]
An antique commode chair - May 29, 2011
I'm a fan of indoor plumbing. That said, this mid-nineteenth-century, American commode chair wouldn't have been a bad alternative (assuming you had a servant to empty the contents). The hole in the seat housed a chamber pot, which was covered by the wooden lid. Then all was hidden by a seat cushion placed on top. Better this than a trip to the privy in bad weather! The chair is on display at the Morris-Jumel Mansion in New York City.
Enteral nutrition for Crohn's disease: comparing formulas - May 22, 2011
Debating which enteral nutrition formula to use? A number of studies have found that amino acid-based ("elemental") and whole protein-based ("polymeric") formulas are equally effective. In the most recent, 93% of children who received an elemental formula and 79% of those who received a polymeric formula reached remission, with the difference between the two groups being statistically insignificant.
Source: Grogan JL, Casson DH, Terry A, Burdge GC, El-Matary W, Dalzell AM. Enteral feeding therapy for newly diagnosed pediatric crohn's disease: A double-blind randomized controlled trial with two years follow-up. Inflamm Bowel Dis. 2011 Mar 18. doi: 10.1002/ibd.21690. [Epub ahead of print]
At the table - May 19, 2011
At last: the ultimate place setting for people with Crohn's disease. As the designer, Leah Piepgras, explains, "the dishes are a map of the digestive tract, from mouth to anus."
The mind-gut connection - May 15, 2011
Surprise: the idea of a mind-gut connection (stress/anxiety = upset tummy) is not a modern development. Alexis de Tocqueville, author of Democracy in America (1835), concluded that he would be a healthier man if he acted more and thought less. "If I ever write a book on medicine," he wrote to his sister-in-law in 1832, "I can tell you it won't be like the ones that usually get published. I'll maintain and prove that in order to be well, you must first of all eat maize and pork, consume a little or a lot or nothing at all according to circumstances, sleep on the floor fully dressed, pass in a single week from icy cold to heat and from heat to icy cold, put your shoulder to a wheel or wake up in a ditch, and, above all, never think. That's the central point: plunge yourself into matter as much as you can, and if possible be like an oyster. I think it was Rousseau who said that a man who thinks is a depraved animal. For myself, I would have said that a man who thinks is an animal with poor digestion."
Source: Translated and quoted in Tocqueville's Discovery of America, by Leo Damrosch (New York: Farrar, Straus and Giroux, 2010): 166.
Fellow travelers - May 8, 2011
Did you know that 90% of your cells don't belong to you at all? They're the cells of bacteria that live on and inside you. Human cells are much larger than bacterial ones so you can't see the microbes that cover every inch of skin and crowd into every nook and cranny of your digestive tract (not to mention colonizing other bits of anatomy as well).
Although we have no bacterial inhabitants in the GI tract at birth, we begin picking them up rapidly from the moment we pass through the birth canal. Isn't it nice to know that we are never really alone? Happy Mother's Day (and best wishes to your bacteria, too)!
Crohn's disease and intestinal cancers - May 8, 2011
Is Crohn's disease a risk factor for intestinal cancers? The authors of a recent analysis found only a modestly increased risk of intestinal cancers in patients with Crohn's, compared with individuals without the disease. However, the Crohn's patients developed colorectal cancer at younger ages (an average of 51.5 years, compared with an average of 71 years in typical populations). Based on these findings, the doctors who performed the analysis recommend that patients with Crohn's have colonoscopies to screen for colorectal cancer beginning at age 40, or once they have had Crohn's for more than 10 years.
Source: Laukoetter MG, Mennigen R, Hannig CM, et al. Intestinal cancer risk in Crohn's disease: a meta-analysis. J Gastrointest Surg. 2011 Apr;15(4):576-83. Epub 2010 Dec 9.
Crohn's disease really gets on your nerves - May 1, 2011
Nerve damage in Crohn's disease? It's not just a side effect of the Flagyl or biologic you've been taking. In nerve conduction studies, patients with IBD who had no obvious symptoms of neurological damage nevertheless were found to have subclinical polyneuropathy. None of the patients had B12 deficiency and they weren't taking any of the drugs typically associated with nerve damage. Chalk it up to one more inflammatory complication of IBD.
Source: Cetinkaya ZA, Cetinkaya Y, Gencer M, et al. The relationship between quiescent inflammatory bowel disease and peripheral polyneuropathy. Gut Liver. 2011 Mar;5(1):57-60.
Thalidomide in Crohn's disease - April 24, 2011
Thalidomide is inching back. For the last dozen years or so, sporadic reports have been published of its use in IBD—most recently the successful treatment of six children with Crohn's. We should soon have a better idea of the drug's potential. A phase III trial is under way in Italy of thalidomide in children and teens with refractory IBD. Based on prior use of the drug, I suspect neuropathy may turn out to be the most challenging side effect. Let's hope its occurrence is low and remission rates are high.
Although thalidomide's mechanism of action is multifaceted, it appears to suppress TNF-alpha and affect the production of interleukins.
Source: Zheng CF, Xu JH, Huang Y, Leung YK. Treatment of pediatric refractory Crohn's disease with thalidomide. World J Gastroenterol. 2011 Mar 14;17(10):1286-91.
Ouch! - April 24, 2011
Do you think it's Crohn's disease?
Hepatosplenic T-cell lymphoma in Crohn's disease: an update - April 19, 2011
Some of you may already have seen the FDA's April 14 update on hepatosplenic T-cell lymphoma (HSTCL) in young patients with Crohn's disease. Here is the link for those who may have missed it. The most interesting finding comes from a careful reading of Table 1, near the end of the report. It shows that cases have been reported after as few as one or two doses of a biologic (mostly given together with an immunomodulating drug). In contrast, none of the HSTCL patients who took azathioprine or 6-MP without a biologic developed the cancer in under three years of use. This could be a statistical blip. But it may also suggest that the more powerful immunosuppression delivered by the biologics, especially when combined with an immunomodulator, places patients at higher risk for this aggressive cancer.
Digestion among the dinosaurs - April 17, 2011
Two and a half weeks to digest your dinner? That's what it took for the sauropods—giant, plant-eating dinosaurs. They gobbled down vegetation without pausing to chew it (they didn't have molars for grinding, only incisors for cropping stems and branches). Tiny bacteria in the gut were left with the massive job of breaking down the plants so nutrients could be absorbed. Galapagos tortoises, which digest food similarly, keep food in their stomach for up to 11 days.
We humans have learned (and evolved) to give digestion a head start. Our food is partially digested before it enters the esophagus—we have a full set of molars for chewing, saliva containing digestive enzymes, and skill at tenderizing foods by cooking, Acidic stomach acid continues the breakdown process. By the time it reaches the intestine, our meal is ready to be sucked up by the villi, after a little extra help from digestive enzymes.
Thanks to this efficient process of decomposition, human gut bacteria are needed mainly in the last stages of digestion, in the large intestine, where they break down any remaining undigestible fiber. Luckily, unlike the sauropods, we're not trying to break down 1,150 pounds of vegetation per day. (I do hope there were no sauropods with Crohn's disease!)
Source: J. N. Wilford. Giants who scarfed down fast-food feasts. N Y Times. 2011 Apr 12: D1+D4.
Pain and bleeding: is it the disease or the drug? - April 10, 2011
Thinking about starting a 5-ASA drug (Pentasa, Asacol, sulfasalazine, etc.)? Approximately 1 in 25 people who do so end up with abdominal pain and bloody diarrhea—not fun! Worse, the reaction isn't always recognized. If a 5-ASA and a steroid are started together, the steroid may "treat" the side effect. Then when the bleeding reappears during the steroid taper, it can be mistaken for a flare of IBD. If possible, wait to start a 5-ASA until you're NOT on steroids.
Source: Swoger JM, Binion DG. Supportive therapy in IBD: what additional diagnoses and conditions must be treated? Dig . 2010;28(3):452-62. Epub 2010 Sep 30.
Admiring the ileum - April 3, 2011
Here's a striking picture of the interior of the ileum. It shows the villi, which are the structures that absorb nutrients. Click on the picture (left) for a larger image. Check out the one on the right, too, showing a single villi close up.
Credits: Professor Giorgio Gabella (left), Liz Hirst (right), Wellcome Images
Extraintestinal symptoms of Crohn's disease - April 3, 2011
For some of us, symptoms outside the GI tract can be worse than those in the gut—and these extraintestinal symptoms are surprisingly common. Among 580 patients with Crohn's, the most common extraintestinal symptoms were arthritis (in 33%), mouth ulcers (10%), uveitis (6%), erythema nodosum (6%), and ankylosing spondylitis (6%). What symptom bothers you most (whether inside or outside the gut)?
Source: Vavricka SR, Brun L, Ballabeni P, et al. Frequency and risk factors for extraintestinal manifestations in the Swiss inflammatory bowel disease cohort. Am J Gastroenterol. 2011 Jan;106(1):110-9. Epub 2010 Aug 31.
From our neighbors to the south - March 27, 2011
Brazil beats US . . . in issuing guidelines for the use of enteral nutrition in Crohn's disease. In children and teens it can be used as a primary treatment to avoid steroids, and in adults it's an alternative for treating refractory Crohn's. US GIs, we need guidelines here, too! In a recent survey of ped GIs in North America, 58% of doctors who did not use EN regularly said they wanted guidelines before considering more frequent use.
Source: Consensus guidelines for the management of inflammatory bowel disease. Arq Gastroenterol (São Paulo). 2010 Jul/Sep;47(3): 313-25.
Low-dose naltrexone for Crohn's disease - March 20, 2011
There's been a lot of buzz about low-dose naltrexone as a potential treatment for Crohn's disease. For those who have been eagerly awaiting an update, a new trial has just been published. I've written an article to give you all the details. Get the scoop right here.
Ovarian Crohn's disease - March 13, 2011
Crohn's disease in the ovaries? Yes, this pesky disease shows up everywhere. The fallopian tubes and ovaries can get fistulas and ulcers that look just like those in the intestines. Ovarian involvement can be an extraintestinal symptom or, alternatively, spread from Crohn's inflammation in neighboring areas of intestine (disease in the terminal ileum or the appendix can affect the right ovary, and disease in the sigmoid colon can involve the left ovary). The symptoms of ovarian Crohn's disease may resemble those of a variety of other conditions, including pelvic inflammatory disease, diverticulitis, appendicitis, and endometriosis.
Source: Ouakaa-Kchaou A, Elloumi H, Kochlef A, et al. Ovarian Crohn's disease. J Crohns Colitis. 2010 Dec;4(6):705-6. Epub 2010 Oct 16.
There is something to be said for modern conveniences - March 6, 2011
Before the age of commercial toilet paper, people wiped with squares cut from paper bags, scrap paper, and flyers. City sewers emptied into rivers, and that's where the paper ended up, too. Those lucky enough to live upriver weren't always aware of this unpleasant fact of life. When Queen Victoria paid a visit to Cambridge, she asked what all those pieces of paper floating in the river were. The Master of Trinity College quick-wittedly produced an innocuous reply: "Those, ma'am, are notices that bathing is forbidden."
Source: Judith Flanders, Inside the Victorian Home: A Portrait of Domestic Life in Victorian England (New York: W. W. Norton, 2003), 338.
Put your parts in place - February 27, 2011
Try this online jigsaw puzzle and see if you can reassemble your digestive system from bits and pieces. (Don't give up when you click on the link and are met with an ad. If you scroll down, you'll see that the puzzle is loading; it will soon replace the ad on the screen.) Have fun!
Adding allopurinol: the ups and downs of another option for IBD - February 27, 2011
To follow-up on last week's post, here's a study of twenty-seven IBDers who used allopurinol in combination with 6-MP or azathioprine. For some, the combo was a real plus: thirteen of the patients (48%) improved, with seven able to stop steroids. On the other hand, fourteen patients had side effects, including five hit with significant infections. It looks like this is worth a try for those needing new options, but—like all drug combinations—will have to be used with caution.
Govani SM, Higgins PD. Combination of thiopurines and allopurinol: adverse events and clinical benefit in IBD. J Crohns Colitis. 2010 Oct;4(4):444-9. Epub 2010 Mar 21.
What if you don't respond to 6-MP? - February 20, 2011
Why do some people respond to 6-MP and others don't—and what can we do about it? Let's take a closer look.
Response seems to depend, at least in part, on how we, as individuals, break down the drug in our bodies. Some people who take 6-MP break it down mainly into substances called 6-thioguanine nucleotides (6-TGN). Others break it down primarily into 6-methylmercaptopurine metabolites (6-MMP). The people who create mostly 6-TGN from 6-MP tend to have fewer side effects and benefit more from the drug than those whose bodies create mostly 6-MMP.
But there may be a way around this, with the help of a drug called allopurinol (best known as a medication for gout). Preliminary research suggests that taking a daily dose of allopurinol during 6-MP treatment can help patients who normally produce mostly 6-MMP (the bad stuff) rather than 6-TGN (the good stuff). In a small study, a group of such patients who were given allopurinol along with 6-MP significantly increased their 6-TGN levels and were able to decrease their dose of 6-MP.
This all seems promising, especially for patients who get side effects every time they try to raise their 6-MP dose to an effective level. The big question will be, does increasing 6-TGN in 6-MP users who don't produce much of it not just reduce side effects from 6-MP, but also lead to higher remission rates and fewer relapses? The concept sounds good, but now we need a big, controlled trial to see whether it works in practice. Here's hoping!
Source: Gerich ME, Quiros JA, Marcin JP, Tennyson L, Henthorn M, Prindiville TP. A prospective evaluation of the impact of allopurinol in pediatric and adult IBD patients with preferential metabolism of 6-mercaptopurine to 6-methylmercaptopurine. J Crohns Colitis. 2010 Nov;4(5):546-52. Epub 2010 May 26.
Fish oil or flax oil? - February 13, 2011
Want to get more omega-3 fatty acids in your diet? Here's a great description of the difference between fish oil and flax oil as sources of omega-3 fatty acids.
Biologics and the baby - February 13, 2011
This one's for moms or future moms who are using any of the biologic drugs. It appears that these medications may pass through the placenta during pregnancy, causing temporary immunosuppression in the baby. For that reason, it may be wise to avoid giving the infant live or attenuated vaccines until at least seven months after birth.
Source: Cheent K, Nolan J, Shariq S, Kiho L, Pal A, Arnold J. Case report: Fatal case of disseminated BCG infection in an infant born to a mother taking infliximab for Crohn's disease. J Crohns Colitis. 2010 Nov;4(5):603-5. Epub 2010 Jun 9.
Your brain on Crohn's - February 6, 2011
Crohn's on your mind? Well, it may actually be IN your mind—in your brain, that is. White matter abnormalities were found in 72% of patients with Crohn's disease, compared with 34% of controls, in a retrospective study. More common in older patients, the white matter lesions may be an extraintestinal manifestation of IBD. Crohn's pops up everywhere, doesn't it?
Source: Chen M, Lee G, Kwong LN, Lamont S, Chaves C. Cerebral white matter lesions in patients with Crohn's disease. J Neuroimaging. 2010 Nov 17. doi: 10.1111/j.1552-6569.2010.00538.x. [Epub ahead of print].
Not just an extra bit of skin - January 30, 2011
Perianal skin tags, anyone? Welcome to yet another complication of Crohn's disease. The skin tags may swell and become painful when the disease is active; in fact, they can be a clue that you've begun to flare. If the tags are troublesome, doctors at the University of Szeged, Hungary, recommend the use of topical tacrolimus.
Source: Molnár T, Nagy F, Wittmann T. Anal skin tag: do not injure the elephants. J Clin Gastroenterol. 2010 Nov-Dec;44(10):722; author reply 722.
Strange but true - January 23, 2011
Tell me what you eat, and I will tell you who you are, said noted epicure Brillat-Savarin. After reading about some of the weird and wonderful objects found in the human digestive tract, I hope he's wrong, or we'd be calling our neighbors anything from cockroaches to cake ornaments. Join me in discovering some of the most unusual items retrieved from the human stomach and intestines. Click here for the full scoop.
Thinking of trying prebiotics? - January 16, 2011
Considering prebiotics? Keep your wallet in your pocket for now. In a large, placebo-controlled study, a prebiotic (15 g per day) didn't reduce symptoms in patients with active Crohn's disease. Also, the patients randomized to the prebiotic were more likely to report gas and a rumbling tummy than those who received the placebo. Unfortunately, for both probiotics and prebiotics, performance has yet to live up to the promise.
Source: Benjamin JL, Hedin CR, Koutsoumpas A, et al. No clinical benefit of prebiotics in the treatment of active Crohn's disease: a double-blind, randomized, placebo-controlled trial [abstract T2020]. Digestive Disease Week 2010, 1-5 May 2010, New Orleans, Louisiana; available online.
The ups and downs of enteral nutrition - January 9, 2011
Every treatment has its ups and downs, and none more so than enteral nutrition. The upside: at two UK hospitals, 78% of the kids who tried EN reached remission. The downside: among those who ultimately relapsed, 60% chose not to use it again. It's a highly effective treatment for those willing to stick with it, but it's not for everyone. A few weeks of steroids or a few weeks of EN: which would you choose?
Source: M Ahmed, WC Davidson, S Roberts. Exclusive enteral nutrition in paediatric Crohn's disease: a multi-site audit [abstract AHP-001]. 43rd Annual Meeting of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition, 9-12 June 2010, Istanbul, Turkey; available online.
A new way to get your B12 - January 9, 2011
B12 users, this one's for you: a potential alternative to monthly injections. Twenty-nine of thirty patients with Crohn's disease were able to switch from injections to high-dose B12 tablets taken orally (1200 mcg once daily). Only a single patient wasn't able to reach normal B12 levels with the tablets. A pill rather than an injection sounds like a great option to me!
Source: Saibil F, Morgan M. Oral B12 in Crohn's disease: is B12 by injection obsolete? [abstract P-0125]. 2010 Advances in Inflammatory Bowel Diseases Crohn's & Colitis Foundation's Clinical &anp; Research Conference, 9-12 December 2010, Hollywood, Florida. Inflamm Bowel Dis 15, Suppl 2, first published online 16 Nov 2009.
A diet that is 90% fat is a good thing? - January 2, 2011
Can you imagine a diet that is 90% fat? Sam Vogelstein, age 9, eats like that every day. The regimen, called the ketogenic diet, is used to control epilepsy. Like enteral nutrition for Crohn's disease, it is one of the few diets proven medically effective in treating a serious chronic disease. Read about Sam's experience in this great article from the New York Times. They also published a letter from me, if you're interested (did you know the Times fact-checks letters?).
Intestinal inflammation discovered in siblings of Crohn's patients - December 26, 2010
Is Crohn's disease a family affair? Researchers found that apparently healthy siblings of Crohn's patients had elevated levels of a protein, fecal S100A12, associated with intestinal inflammation. So far we don't know if this mild inflammation is a risk factor for Crohn's. At least none of the siblings have developed the disease in the two years since the study was performed.
Pham M, Leach ST, Lemberg DA, Day AS. Subclinical intestinal inflammation in siblings of children with Crohn's disease. Dig Dis Sci. 2010 Dec;55(12):3502-7. Epub 2010 Oct 8.
Some attention for Beat Crohn's! - December 21, 2010
Any CCFA members out there? There is a nice review of Beat Crohn's on page 19 of the current issue of the CCFA's magazine, Take Charge. I'm doing a happy dance tonight!
Holy moly, our guts are holey! - December 19, 2010
Get out the patch kit, Crohnies really do have leaky guts! As part of the normal life cycle of cells, a tiny hole appears in the intestinal wall (epithelium) wherever an old epithelial cell is shed. It turns out that people with Crohn's disease have more of these itsy bitsy gaps in their epithelium than non-Crohnies. Inflammation is the likely culprit, causing increased shedding of epithelial cells.
Source: Liu JJ, Madsen KL, Boulanger P, Dieleman LA, Meddings J, Fedorak RN. Mind the gaps: confocal endomicroscopy showed increased density of small bowel epithelial gaps in inflammatory bowel disease. J Clin Gastroenterol. 2010 Oct 27. [Epub ahead of print]
The strange case of sulfasalazine - December 12, 2010
Have you ever taken sulfasalazine (also called Azulfidine, Sulfazine, Salazopyrin, and a few other names)? It works in a very curious way. It contains an antibiotic that prevents bacteria from producing folic acid, which they need to copy their DNA and reproduce. As Sam Kean phrases it, instead of a "bacteria killer," it's "bacteria birth control!"
Actually, it's birth control for human cells, too, but we can get folic acid from supplements instead. Bacteria can't chomp along with us; they have to make their own folic acid.
Source: Sam Kean, The Disappearing Spoon and other True Tales of Madness, Love, and the History of the World from the Periodic Table of the Elements (New York: Little, Brown and Company, 2010), 180.
Crohn's at the zoo? - December 6, 2010
At the San Francisco Zoo, keepers are waiting for the results of a capsule endoscopy on a gorilla, 29-year-old Zura. She gobbles down anything that falls in her enclosure, from purses to cell phones. Doctors aren't sure if her chronic GI problems are caused by her eating habits or Crohn's disease. She gets diarrhea, constipation, and bloating—sound familiar? Don't miss the video.
Healthier bones for patients with Crohn's - December 5, 2010
Have you been told that you have bone loss from Crohn's disease? It's a common side effect, whether from malabsorption, steroid use, or simply inflammation from the disease. But here's some good news from a recent study. Bone loss decreased and bone formation increased in kids with Crohn's who were treated with enteral nutrition (without any other medications). Seventy percent of the children went into remission, too. It's likely the effects on bone would be similar for adults, but mainly pediatric GIs are studying enteral nutrition, meaning that most of the current studies involve kids.
Source: Whitten KE, Leach ST, Bohane TD, Woodhead HJ, Day AS. Effect of exclusive enteral nutrition on bone turnover in children with Crohn's disease. J Gastroenterol. 2010 Apr;45(4):399-405. Epub 2009 Dec 3.
Gene mutation found in two babies with IBD - December 5, 2010
Can infants have IBD? They sure can. Two babies with severe, treatment-resistant IBD, both under a year old, were found to have a previously undocumented mutation in the interleukin-10 gene. The mutation interfered with the gene's ability to suppress the release of an inflammatory protein, TNF-alpha. Isn't it sad to think of tiny babies having to suffer from fistulas and the like?
Glocker EO, Frede N, Perro M, Sebire N, Elawad M, Shah N, Grimbacher B. Infant colitis—it's in the genes. Lancet. 2010 Oct 9;376(9748):1272.
Risks of biologics may be higher in older patients - November 28, 2010
Over age 65 or know a Crohn's patient who is? The authors of a recent study suggest that biologic drugs be used cautiously in older patients. Among IBD patients over age 65 treated with Remicaid or Humira, deaths and severe infections were significantly more common than in biologic users under 65. Also, elderly biologic users were more likely to have a serious infection or to die than elderly patients treated with other medications for IBD (most often steroids plus azathioprine).
In light of these findings, the less frequent prescribing of biologics to older patients (reported in the study I summarized in my post of October 31) may turn out to be a good thing.
Source: Cottone M, Kohn A, Daperno M, et al. Age is a risk factor for severe infections and mortality in patients given anti-tumor necrosis factor therapy for inflammatory bowel disease. Clin Gastroenterol Hepatol. 2010 Oct 14. [Epub ahead of print]
Our puzzling guts - November 21, 2010
Do you know where YOUR guts are? Try this puzzle and find out! You have to fit all your organs into the abdomen in the right place. The intestines are easy, but what about the other ephemera? The pancreas or spleen, for example? You can repeat the puzzle as often as you want. I guarantee you will have a better grasp on your interior anatomy when you're finished.
Few U.S. gastroenterologists prescribe enteral nutrition - November 14, 2010
Judging from a recent survey, we have a long way to go before enteral nutrition is fully accepted as a treatment for Crohn's. Pediatric GIs in North America were asked whether they prescribed total enteral nutrition to treat Crohn's disease. In the U.S., only 9% said they used it regularly in their practice (vs. 32% in Canada), and five times as many U.S. as Canadian GIs said they never prescribed it. Doctors cited compliance as the biggest challenge of enteral nutrition use, and avoiding or reducing steroid use as the biggest benefit.
Source: Stewart M, Day AS, Otley A. Physician attitudes and practices of enteral nutrition as primary treatment of paediatric crohn disease in North America. J Pediatr Gastroenterol Nutr. 2010 Oct 20. [Epub ahead of print]
Can't go? - November 14, 2010
There's something to be said for living in the twenty-first century. Case in point: during the Renaissance, the element antimony was made into pills to use as a laxative. Since antimony passes through the intestines without dissolving, patients searched their stool for the pills to reuse them! Your expensive laxative might even be reemployed by someone else. (DON'T try this one at home. Antimony, we know today, is toxic.)
Source: Sam Kean, The Disappearing Spoon and other True Tales of Madness, Love, and the History of the World from the Periodic Table of the Elements (New York: Little, Brown and Company, 2010), 22.
Dealing with strictures - November 7, 2010
Ever had a stricture dilated? A new study suggests that injecting a corticosteroid into the stricture at the time of the dilation might keep the area open longer. In the study, children were randomly assigned to endoscopic balloon dilation accompanied by a steroid injection (15 patients) or dilation in conjunction with a placebo injection (14 patients). A year later, none of the patients given the steroid injection had needed surgery and only one had had to have a repeat dilation. In contrast, five of the children who received the placebo injection needed a repeat dilation, with four of the five subsequently requiring surgery. Sounds good! Further investigation would be welcome, however, since the study was relatively small.
Di Nardo G, Oliva S, Passariello M, et al. Intralesional steroid injection after endoscopic balloon dilation in pediatric Crohn's disease with stricture: a prospective, randomized, double-blind, controlled trial. Gastrointest Endosc. 2010 Oct 16. [Epub ahead of print]
Biologic treatment more likely in patients diagnosed at younger ages - October 31, 2010
Among patients with Crohn's disease treated at a Veterans Affairs hospital during the last 10 years, those diagnosed at a younger age were significantly more likely to be treated with biologics than those diagnosed when they were older. This was true even AFTER controlling for disease severity. Strikingly, "with every year older at diagnosis, patients were 4% less likely to be biologic users." The patients ranged in age from 20 to 87.
Although some data suggested that the patients diagnosed at younger ages tended to have more severe disease, this finding was by no means conclusive. Although a clinician might be more reluctant to prescribe a biologic for an older patient already taking several drugs, it's not impossible that doctors are subconsciously favoring more aggressive treatments for patients diagnosed at younger ages and less aggressive treatments for those diagnosed later in life.
Source: Feagins LA, Spechler SJ. Biologic agent use varies inversely with age at diagnosis in Crohn's disease. Dig Dis Sci. 2010 Sep 16. [Epub ahead of print]
Wondering about that annoying tickle in your throat? - October 24, 2010
Warning: if you're squeamish, you may find this report a bit gross. But believe me, it's a story you won't have heard before!
A patient was anemic and had a tickle in his throat. The doctor decided to do an upper endoscopy to see what might be going on. Turned out there was a leech in there, feeding on the man's throat! He had a habit of drinking water from a spring, which was the most likely source for the leech.
You'll be happy to learn that the leech was removed and the patient recovered.
Source: Coban S, Tutal E, Alpay D, Köklü S. An unexpected cause of severe anemia in an adult patient: a pharyngeal leech (with video). Gastrointest Endosc. 2010 Sep 24.[Epub ahead of print]
Will you relapse if you discontinue Remicaid? - October 24, 2010
If you're in remission on Remicaid, should you risk stopping the drug? Among 48 patients who did so, two-thirds ultimately relapsed (half within the first 16 months after discontinuing treatment). On the other hand, 35% of those who discontinued the drug DIDN'T relapse. They were still in remission after a median follow-up period of 4.1 years.
The researchers didn't find any factors, such as disease location, that could help us predict which patients will stay in remission after stopping treatment. But it's nice to know that at least some will.
Source: Waugh AW, Garg S, Matic K, et al. Maintenance of clinical benefit in Crohn's disease patients after discontinuation of infliximab: long-term follow-up of a single centre cohort. Aliment Pharmacol Ther. 2010 Aug 30. doi: 10.1111/j.1365-2036.2010.04446.x. [Epub ahead of print]
Developing new drugs to treat Crohn's disease is a risky business - October 17, 2010
Lots of medications are tested for Crohn's disease, but only a handful end up on the pharmacy shelf. Researchers studied Phase 1, 2, and 3 clinical trials, conducted in the US between 1998 and June 2008 to test new medications for moderate-to-severe Crohn's disease. Although 92% of the Phase 1 trials were successful, most of the drugs evaluated in these initial trials crashed and burned during the subsequent development process. Just 18% of those that began development progressed through the entire testing process and were approved by the US FDA.
The challenges of drug development are probably even greater than these results suggest. The three drugs that reached the market (Tysabri, Humira, and Cimzia) were all "me too" drugs—medications in many ways similar to a product already on the market (Remicaid), rather than products in a completely new class.
Source: Parker JL, Clare Kohler J. The success rate of new drug development in clinical trials: Crohn's disease. J Pharm Pharm Sci. 2010;13(2):191-7.
The latest in Byzantine toilets - October 14, 2010
Toilet seat too cold for you? You're lucky you aren't sitting on this latrine in Israel, dating from the Byzantine era. Visitors perched on two of the stone rods in order to do their business. Waste dropped between the rods into the trough below. The narrow channel in front held running water to moisten the toilet paper of the day: sea sponges fastened to sticks.
Photo (by Kay Axhausen, Zurich, Switzerland) and info from: sewerhistory.org
Enteral nutrition for growth and remission - October 10, 2010
Enteral nutrition gets a nod in an article about nutrition in kids with IBD. The authors, who are affiliated with Seattle Children's Hospital, write: "A number of randomized trials suggest that primary EEN [exclusive enteral nutrition] therapy not only achieves remission rates comparable to corticosteroids in children but also improves growth compared with patients receiving corticosteroids. EEN has been shown to be effective also in maintaining remission of IBD."
It's great to see some support for enteral nutrition in the US!
Source: Mallon DP, Suskind DL. Nutrition in pediatric inflammatory bowel disease. Nutr Clin Pract. 2010 Aug;25(4):335-9.
Psoriasis, eczema, and the biologics - October 3, 2010
You've probably heard that psoriasis and eczema can show up as side effects of the biologic drugs. Luckily it turns out that doesn't happen very often. Doctors who studied these skin conditions in IBD patients treated with Remicaid, Humira, or Cimzia estimate that around 5% of IBD patients treated with the drugs will develop psoriasis-like or eczema-like lesions. But only an estimated 1% will have to discontinue treatment because of the skin problems.
In the study, risk of developing psoriasis-like or eczema-like lesions when using biologics was highest in women and in people with a personal or family history of psoriasis or allergic conditions (e.g. asthma, eczema, or hay fever). Unfortunately for those affected, it appears that switching to a different biologic almost never clears up the drug-induced lesions, but they'll go away if biologic treatment is stopped.
Source: Rahier JF, Buche S, Biroulet LP, et al. Severe skin lesions cause patients with inflammatory bowel disease to discontinue antitumor necrosis factor therapy. Clin Gastroenterol Hepatol. 2010 Aug 20. [Epub ahead of print]
Surgery for rectovaginal fistulas - September 26, 2010
Here's a report from a group of surgeons who treat rectovaginal fistulas. Their patients included 77 women whose fistulas were caused by Crohn's disease. Ultimately 78% of the fistulas in these women healed successfully, but the process often took more than one surgery—an average of 1.8 operations per healed fistula. One tip: because tobacco smoking almost doubled the risk that a rectovaginal fistula would recur, the authors encourage women to stop smoking before having surgery on a fistula.
Source: Pinto RA, Peterson TV, Shawki S, et al. Are there predictors of outcome following rectovaginal fistula repair? Dis Colon Rectum. 2010 Sep;53(9):1240-7.
IBS or IBD? - September 19, 2010
Can people with IBD also have irritable bowel syndrome, or are their "IBS" symptoms actually simmering IBD? Finally we have a study addressing just that issue! Doctors in Ireland measured levels of fecal calprotectin (a marker of intestinal inflammation) in patients with IBD who were in clinical remission. Some of the IBD patients had "IBS" symptoms and others did not. The doctors also measured fecal calprotectin levels in two control groups: healthy women and women with IBS.
Patients who had IBD plus IBS symptoms had the highest mean levels of fecal calprotectin (Crohn's disease + IBS, 414.7 mg/kg; ulcerative colitis + IBS, 591.1 mg/kg). IBD patients without IBS symptoms had lower, but still elevated, levels (CD + IBS, 174.9; UC + IBS, 229.8). The control groups, in contrast, had minimal levels of fecal calprotectin (23.7 for the healthy women and 24.7 for the women with IBS). The authors' conclusion: IBS symptoms in IBD patients "reflect ongoing, although subclinical activity of IBD and their presence should always be interpreted as such."
Source: Keohane J, O'Mahony C, O'Mahony L, et al. Irritable bowel syndrome-type symptoms in patients with inflammatory bowel disease: a real association or reflection of occult inflammation? Am J Gastroenterol. 2010 Aug;105(8):1788, 1789-94; quiz 1795. Epub 2010 Apr 13.
The Victorian toilet - September 15, 2010
Tired of boring bathroom fixtures? The Victorians had the right idea. Late-nineteenth-century toilets were decorated with an amazing range of patterns: architectural and geometrical motifs; fruit, flowers, ribbons, and shells; birds and fish; and so forth. Even luxury pottery manufacturers such as Wedgewood got into the toilet-bowl business. Originally the ornament was only on the inside of the bowl, but soon fashion dictated covering the outside as well. Here's a fine example! Be sure to scroll down on that page to admire the views of the interior.
Source: Judith Flanders, Inside the Victorian Home: A Portrait of Domestic Life in Victorian England (New York: W. W. Norton, 2003), 332-33.
Should fathers stop immunosuppressives before trying to conceive? - September 12, 2010
Here's one for the gentleman who are considering parenthood—a report on pregnancies fathered by men with IBD. Fathers were divided into two groups: men using 6-MP or azathioprine at any point during the three months prior to conception and men not using either drug when trying to conceive. Happily, there were no significant differences between the two groups in preterm births, babies with congenital malformations, babies with low birth weight, or unsuccessful pregnancies (spontaneous abortions, ectopic pregnancies, blighted ovum pregnancies, and fetal death). These results suggest that it is not necessary for men treated with 6-MP or azathioprine to discontinue either medication before fathering a child. Although it is impossible to rule out the possibility that a larger study might identify side effects from using these drugs during conception, this is still the biggest published study of its type, including 130 pregnancies fathered by 84 men.
Source: Teruel C, Román AL, Bermejo F, et al. Outcomes of pregnancies fathered by inflammatory bowel disease patients exposed to thiopurines. Am J Gastroenterol. 2010 Sep;105(9):2003-8. Epub 2010 Aug 10
Healthy babies for women with Crohn's - September 7, 2010
Here's some good news for women with Crohn's disease who are considering pregnancy. Researchers reviewed 871,579 births to first-time moms, including 2,377 births to mothers with Crohn's. There were NO significant differences between women with and without Crohn's in rates of preeclampsia, stillbirths, congenital malformations, or poor five-minute Apgar scores. (Apgar scores measure the health of a newborn baby.) Women with Crohn's disease did have a higher risk for preterm birth, cesarean sections, and babies who were small for their gestational age. But overall, these results suggest that women with Crohn's can look forward to healthy babies—babies who are no more likely to have birth defects than children of moms without IBD.
Source: Stephansson O, Larsson H, Pedersen L, Kieler H, Granath F, Ludvigsson JF, Falconer H, Ekbom A, Sørensen HT, Nørgaard M. Crohn's disease is a risk factor for preterm birth. Clin Gastroenterol Hepatol. 2010 Jun;8(6):509-15. Epub 2010 Mar 2.
Enteral nutrition as a maintenance therapy - August 29, 2010
How much enteral nutrition should you use to maintain remission? The more the better, according to Watanabe and colleagues. In a study of 268 patients with Crohn's disease, those who used 900 calories or more of enteral nutrition per day were significantly less likely to be hospitalized than those who used lesser amounts.
Source: Watanabe O, Ando T, Ishiguro K, et al. Enteral nutrition decreases hospitalization rate in patients with Crohn's disease. J Gastroenterol Hepatol. 2010 May;25 Suppl 1:S134-7.
Natural curiosities - August 22, 2010
I have just been reading a fascinating essay about, of all things, dung beetles. Some varieties have a curious courtship ritual. Mr. Dung Beetle tears off a juicy bit of feces, rolls it into a ball, and waves it in front of the Ms. Dung Beetle of his choice. Hey, whenever works for you…
By the way, think kindly of dung beetles. If it weren't for them, we'd be up to our necks in mammal poop. They feed on it and bury the remains underground, fertilizing and aerating the soil in the process.
Source: Natalie Angier, "In recycling waste, the noble scarab is peerless," in The New York Times Book of Insects, ed. by Nicholas Wade (Guilford, CT: The Lyons Press, 2003), 7-15.
A third biologic - August 15, 2010
Thinking about trying a third biologic drug? Allez and colleagues report data on European adults who received adalimumab (Humira) or certolizumab pegol (Cimzia) after not responding to, losing response to, or becoming intolerant to two other anti-TNF drugs. Considering that the 67 patients studied had already been treated with two biologics, it was encouraging that 61% had responded to their third anti-TNF drug at week 6 and 51% were responders at week 20. (Response meant that the patients showed improvement but were not necessarily in full remission.)
That said, only 15 patients (22%) were in remission and off steroids at week 20. In addition, the safety data were sobering. Two patients died while being treated with their third biologic (sudden death in a 37-year-old man with no risk factors for heart disease, and a fatal central line infection in a woman hospitalized for acute obstruction). Also observed were a severe pulmonary infection, a bout of heart failure (reversible after withdrawing the medication), and psoriasis or psoriasis-like lesions in five patients, four of whom had to discontinue the drug.
Conclusions? If you are running out of treatment options, there is a decent chance of response to a third biologic. But the potential benefit has to be weighed against the risk of side effects.
Source: Allez M, Vermeire S, Mozziconacci N, et al. The efficacy and safety of a third anti-TNF monoclonal antibody in Crohn's disease after failure of two other anti-TNF antibodies. Aliment Pharmacol Ther. 2010 Jan;31(1):92-101
Vitamin D - August 12, 2010
Many patients with Crohn's disease have low levels of vitamin D. Might taking vitamin D supplements help control the disease? Jørgensen and colleagues put it to the test. Patients with Crohn's disease in remission were randomly assigned to a year of daily treatment with 1200 international units of vitamin D3 or a placebo. The patients in both groups also took 1200 mg per day of calcium. During the course of the year, six of the 46 patients who received vitamin D relapsed (13%), compared with 14 of the 48 who received the placebo (29%). But don't start shopping for vitamin D yet. The difference between the two groups was NOT statistically significant, meaning that we CANNOT conclude that vitamin D supplementation decreases relapse rates. The lower percentage of relapses in the vitamin D group could have occurred by chance.
Find that hard to accept, after looking at the percentage differences? Many people do. Try considering how you would feel if the results were reversed: if 29% of the patients who received vitamin D had relapsed, compared with only 13% of those who received the placebo, and the difference between the two groups was not statistically significant. Would you be less likely to rush out and buy vitamin D? Yet this would be the exact same result: no proven differences between the treatment and the placebo.
Source: Jørgensen SP, Agnholt J, Glerup H, et al. Clinical trial: vitamin D3 treatment in Crohn's disease - a randomized double-blind placebo-controlled study. Aliment Pharmacol Ther. 2010 Aug;32(3):377-83. Epub 2010 May 11.
Gluten-free diets - August 10, 2010
It seems that an increasing number of patients with IBD are experimenting with gluten-free diets. If you're one of them, make sure your overall diet is still nutritionally sound. A study of British patients with celiac disease found that both men and women eating a gluten-free diet tended to consume little dietary fiber. Their carbohydrates came mainly from sugary foods. Many also failed to meet recommended daily requirements of vitamins and minerals, including calcium, magnesium, zinc, selenium, and manganese. The authors' advice? If you follow a gluten-free diet, eat more beans, pulses, and starchy vegetables such as potatoes and sweet potatoes, and choose fiber-rich grains like quinoa.
Source: Wild D, Robins GG, Burley VJ, Howdle PD. Evidence of high sugar intake, and low fibre and mineral intake, in the gluten-free diet. Aliment Pharmacol Ther. 2010 Aug;32(4):573-81. Epub 2010 Jun 4.
Enteral nutrition in children - August 4, 2010
I'll try and keep you current with the latest research on all the available treatments for Crohn's disease. But of course I have a soft spot for enteral nutrition, so I'm pleased to report that it has received special mention in a review of nutrition in pediatric IBD. The authors (Dr. Maria Oliva-Hemker at Johns Hopkins and Dr. Laurie S. Conklin at Children's National Medical Center in DC) write: "With a demonstrated equivalent efficacy to corticosteroids at inducing remission, exclusive enteral feeding may be a better option for pediatric patients, given the known detrimental effects of corticosteroids on growth and bone development. Particularly in pediatrics, parents may opt for attempting enteral therapy over a more 'top-down approach' owing to concerns about potential serious medication side effects, such as lymphoma."
Source: Conklin LS, Oliva-Hemker M. Nutritional considerations in pediatric inflammatory bowel disease. Expert Rev Gastroenterol Hepatol. 2010 Jun;4(3):305-17.
Mesalamine or azathioprine after surgery - August 3, 2010
After surgery, what's the best choice of maintenance therapy for Crohn's disease? In a recently published double-blind study, 78 patients who had just had a resection were randomly assigned to receive azathioprine or mesalazine for a year. (The preparation of mesalazine used was Salofalk, which releases mesalazine—called mesalamine in U.S.—in the terminal ileum and colon.)
Neither drug was a clear winner. Although none of the patients who received azathioprine, compared with four in the mesalazine group, suffered a relapse or discontinued the drug because it wasn't working, those in the azathioprine group were more likely to stop treatment due to side effects (24% vs. 3%). Another finding was that the azathioprine-treated patients were significantly more likely to have endoscopic improvement at the end of the year (63.3% vs. 34.4% in the mesalazine group). Once again we have the usual treatment dilemma: better efficacy usually comes with a higher risk of side effects.
Source: Reinisch W, Angelberger S, Petritsch W, et al. Azathioprine versus mesalazine for prevention of postoperative clinical recurrence in patients with Crohn's disease with endoscopic recurrence: efficacy and safety results of a randomised, double-blind, double-dummy, multicentre trial. Gut. 2010 Jun;59(6):752-9.
Methotrexate in Crohn's disease - July 30, 2010
There aren't a lot of studies of methotrexate in patients with Crohn's disease, probably because most who start on an immunomodulating drug begin with 6-MP or azathioprine. However, here is some new data for those considering methotrexate.
Doctors at the gastroenterology unit of a German hospital examined the records of their patients with Crohn's disease. Among 63 who had received methotrexate at some point between December 2000 and January 2009, (79%) were in remission after three months of treatment. Those treated with methotrexate alone (24 of the patients) were just as likely to be in remission after three months as those who took methotrexate together with an infliximab (Remicaid) induction regimen (27 patients) and those who took methotrexate in conjunction with prednisolone (a steroid) (12 patients). That said, this was a retrospective rather than a randomized study, and those who were given infliximab or the steroid might have been more severely ill than those given only methotrexate.
The disadvantage of methotrexate was that 21 of the 63 patients (33%) had to discontinue the drug sooner or later because of side effects. In fact, seven discontinued treatment within the first three months. But there is no perfect treatment for Crohn's, and it is nice to have additional information about one of the established options.
Source: Hausmann J, Zabel K, Herrmann E, Schröder O. Methotrexate for maintenance of remission in chronic active Crohn's disease: long-term single-center experience and meta-analysis of observational studies. Inflamm Bowel Dis. 2010 Jul;16(7):1195-202.
IBD and colorectal cancer risk - July 28, 2010
Patients with ulcerative colitis are known to be at increased risk for colorectal cancer. But what about patients with Crohn's disease? Are they also an increased risk? Bergeron and colleagues have conducted a very useful study to look at just this issue. They examined rates of neoplasia (i.e., abnormal cells that can lead to cancer) among 875 patients enrolled in an IBD registry. All of the patients had had at least one episode of pancolitis (disease throughout the colon, with or without rectal involvement). There were 523 patients with Crohn's disease, 276 with ulcerative colitis, and 56 with indeterminate IBD (the latter were grouped together with the ulcerative colitis patients).
The cumulative risk over 25 years for advanced neoplasia (defined as high-grade dysplasia or invasive cancer) was 25.9% for patients with ulcerative colitis and only 3.9% for those with Crohn's. Quite a difference, wouldn't you say?
Confused? Another way of phrasing this is to say that after the passage of 25 years, the probability of the ulcerative colitis patients having advanced neoplasia was 25.9%, and the probability of those with Crohn's having advanced neoplasia was 3.9%.
Notably, in the patients with Crohn's disease, the endoscopic appearance of the colon turned out to have a significant effect on risk. The 25-year cumulative risk of advanced neoplasia was 10.6% for Crohn's patients with ulcerative colitis-like intestinal involvement and just 1.5% for Crohn's patients whose colon didn't have a UC-like appearance. To be classified as UC-like, the intestinal lining (mucosa) had to show continuous and homogeneous disease involvement in at least one segment of the colon.
What are the main lessons we can learn from this study? First, if you have ulcerative colitis or indeterminate colitis, keep getting those screening colonoscopies! Second, if you have Crohn's disease, talk with your doctor about your colonoscopy results. Your need for regular screenings may depend on whether you have ever had "UC-like" areas in your colon.
Source: Bergeron V, Vienne A, Sokol H, et al. Risk factors for neoplasia in inflammatory bowel disease patients with pancolitis. Am J Gastroenterol. 2010 Jun 15. [Epub ahead of print]
Cimzia - July 26, 2010
Are you wondering if it would be worth trying Cimzia (certolizumab)? Encouraging results are available from a small study. Schoepfer and colleagues prospectively collected data on Swiss patients treated with Cimzia after its approval in Switzerland in September 2007. Among 50 patients treated with Cimzia by February 20, 2009 (when the data-collection period ended), 40% were in remission after six weeks of treatment. This is a relatively high success rate, considering that the patients seem to have had severe disease. Over half had already had surgery related to Crohn's; 78% had tried Remicaid and 50% Humira; and all but two had used azathioprine or 6-mercaptopurine.
I'd love to see a formal study of enteral nutrition in patients who had failed at least one biologic. It would be interesting to see how the remission rates compare.
Source: Schoepfer AM, Vavricka SR, Binek J, et al. Efficacy and safety of certolizumab pegol induction therapy in an unselected Crohn's disease population: results of the FACTS survey. Inflamm Bowel Dis. 2010 Jun;16(6):933-8.
Is Crohn's an autoimmune disease? - July 23, 2010
Is Crohn's an autoimmune disease? In an article in last week's Lancet, Behr and colleagues argue that the case is far from proven. They point out that autoantibodies (antibodies against our own tissues) are common in patients with ulcerative colitis, but are found far less frequently in people with Crohn's. They postulate that Crohn's disease is more likely to be caused by 1) an immune deficiency or 2) an immunological reaction to disturbances in the bacterial flora of the intestines. No answers yet…but the research continues!
Source: Behr MA, Divangahi M, Lalande JD. What's in a name? The (mis)labelling of Crohn's as an autoimmune disease. Lancet. 2010 Jul 17;376(9736):202-3.
What do you worry about? - July 22, 2010
What do you worry about when it comes to Crohn's disease? For Swedish adults with active Crohn's who participated in a recent study, the number one concern—by a substantial margin—was having to have an ostomy bag. Other common worries, in descending order of concern, were energy level, loss of bowel control, effects of medication, having surgery, and pain or suffering. In contrast with patients who were flaring, patients in remission weren't terribly worried about any of these issues, although ostomy remained the biggest concern.
How about you? What are your big concerns when it comes to Crohn's disease?
Source: Stjernman H, Tysk C, Almer S, et al. Worries and concerns in a large unselected cohort of patients with Crohn's disease. Scand J Gastroenterol. 2010 Jun;45(6):696-706.
Do the biologics reduce hospitalization risk? - July 17th, 2010
I spotted an interesting study from late 2009. The authors looked at U.S. hospitalization rates for IBD patients. They chose an eight-year period beginning in 1998, the year Remicaid (infliximab) reached the US market. They wanted to see if the availability of the drug reduced the need for surgery for IBD. Surprisingly enough, they found no signs that it had. Rates of hospitalization for IBD-related surgery didn't change over the eight-year period. This was also true when they considered patients with Crohn's disease and ulcerative colitis separately. Take-home message: using Remicaid may not decrease the risk of needing surgery for Crohn's disease or ulcerative colitis.
Source: Cannom RR, Kaiser AM, Ault GT, et al. Inflammatory bowel disease in the United States from 1998 to 2005: has infliximab affected surgical rates? Am Surg. 2009 Oct;75(10):976-80.
Elephants and us - July 18, 2010
Elephants eat plants, trees, and shrubs. Thanks to all this fiber, which is only partially digested, they poop some 17 times per day—more than 300 pounds worth of "deposits" in 24 hours! Can we name them honorary Crohnies?
Source: George Poinar Jr. and Roberta Poinar. What Bugged the Dinosaurs? Insects, Disease, and Death in the Cretaceous. Princeton: Princeton University Press, 2008.
The curious koala - July 16, 2010
Cute little koalas smell like cough drops because they eat so many eucalyptus leaves! (Just as well we humans mostly don't smell like what we eat—it would be nice after a chocolate bar, not so nice after that tasty filet of salmon!)
Source: "Koala. Amazing Animals of the World." Grolier Online (accessed July 16, 2010).
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About the Blogger:
Margaret A. Oppenheimer, the author of this blog, has more than ten years of experience as a medical writer. When not digging up the latest news about Crohn's disease, she enjoys reading, visiting museums, and chatting with her computer—she does all her computer work using voice-recognition software.
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