Sunday, November 24, 2013

IBD and Travel

 Travelling with Crohn's Disease and Ulcerative Colitis


Tis the season … to travel.  Many of us will be travelling in November and December to visit friends and relations, or to take some long-needed vacation hours before they go away at the end of the year.  Travelling with IBD is different than travelling for others without the disease.  There are many sites good travel tips for those with IBD, ranging from getting extra meds to obtaining records from your doctor to finding restrooms.  Here are a few good links:

My own travel tip is to make use of hotel bathrooms.  They tend to be clean, readily accessible off the lobby, open 24 hours, and open to anyone who stops (its hard to know who is a guest and who isn’t).  But this site is above evidence-based IBD.  Are there increased risks for those with Crohn’s and Ulcerative Colitis?  How about hard numbers?  Fortunately, there has been some research into just these questions.

First off, travel has a bigger impact on individuals with IBD.  In a study of Crohn’s patients in remission, they found that 20.5% ended up with diarrhea while traveling, compared with 1.3% of healthy controls. Approximately 6% ended up in a flare post-travel. (1)  A second, larger study found a similar increase in risk with all IBD patients (both Crohn’s and UC), though not as extreme, finding that illness occurred in 15.1% of trips made by patients with IBD compared with 10.9% for controls.  This study differentiated travel in the developing world, and found that travel to high risk locations had equal risk for those with IBD, but travel to more industrialized areas put those with IBD at higher risk due to the underlying illness (and not local conditions).(2)

The second area that travel can have an impact is vaccinations – specifically international travel.  Those with IBD taking steroids, immunomodulators, or anti-TNF-alpha drugs are considered immunocompromised.  They should be vaccinated using any inactivated (dead virus) vaccines but not live virus vaccines prior to travel.(3)  There are two reasons that are given for avoiding live virus vaccines – 1) the efficacy may not be as great, 2) there may be a negative systematic response.  The first risk exists with any vaccine – the second only with live virus vaccines (Yellow Fever vaccine being the most often cited for travel reasons).  Despite the guidance provided, there is minimal evidence that rates of systemic infection are higher for those on anti-TNF-alpha drugs – this area requires further research, but avoidance of areas with endemic disease and the required vaccinations is the safer route until it occurs.

A final area of interest and the subject of recent research is high altitude travel (both in a plane and at higher altitude locations).  It is known that hypoxia can increase inflammation, and higher altitude environments can induce hypoxia in those not acclimated.  A research study out of Switzerland found an almost doubled risk of flare in IBD patients within four weeks of high altitude adventures (though pressurized, airplane cabin pressures are generally equivalent to an 8,000 foot altitude at their lowest pressure).  While avoiding air travel isn’t practical, individuals should be aware of the increased risk possible based on the preliminary data from this study.(4)  This may be the partial cause of the increased diarrhea and exacerbated illness risks noted above.

Whatever your travel plans, I wish everyone a fun an healthy holiday season.

Bottom Line


·         Those with IBD may have increased risk of diarrhea with travel.
·         Prolonged air travel or high-altitude vacation destinations may induce flares.
·         Live virus vaccines should be avoided, but more research needs to be done to confirm this.
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1.       Ellul, Pierre, Valerie Anne Fenech, Christine Azzopardi, Lara Callus, Nicholas Delicata, Jeffrey Muscat, Neville Azzopardi, and Mario Vassallo. "Diarrhoeal episodes in travellers suffering from IBD." Frontline Gastroenterology 4, no. 2 (2013): 120-124.
2.       Ben–Horin, Shomron, Yoram Bujanover, Shulamit Goldstein, Moshe Nadler, Alon Lang, Uri Kopylov, Lior Katz, Adi Lahat, Eli Schwartz, and Benjamin Avidan. "Travel-associated health risks for patients with inflammatory bowel disease." Clinical Gastroenterology and Hepatology 10, no. 2 (2012): 160-165.
3.       Wasan, Sharmeel K., Jennifer A. Coukos, and Francis A. Farraye. "Vaccinating the inflammatory bowel disease patient: deficiencies in gastroenterologists knowledge." Inflammatory Bowel Diseases 17, no. 12 (2011): 2536-2540.
4.       Vavricka, Stephan R., Gerhard Rogler, Sandra Maetzler, Benjamin Misselwitz, Ekaterina Safroneeva, Pascal Frei, Christine N. Manser et al. "High altitude journeys and flights are associated with an increased risk of flares in inflammatory bowel disease patients." Journal of Crohn's and Colitis (2013).

Sunday, November 17, 2013

Backdoor to your Soul

Eyes and IBD

One of the lesser known extraintestinal impacts of Crohn’s Disease and Ulcerative Colitis is on the eyes.  Because of the potential impact on vision, those with IBD should make sure they see an eye doctor for a regular exam (annually) to baseline and then monitor their vision.  In addition to the diseases themselves, certain drugs used to treat IBD have a negative impact on vision long-term.  Understanding the risks can assist in early detection of problems and intelligent choices in medication.
Overall ocular inflammation is much higher in IBD than in the general population.  The estimated rate of occurrence is currently between 4% and 12% of IBD sufferers that develop ocular manifestations.(1)  The two primary categories of inflammation not related to drugs are uveitis and scleritis.  A small study showed a much higher incidence of both occurring with colonic involved disease than with isolated small bowel disease, finding that “Patients with colitis or ileocolitis were more likely to suffer from ocular inflammation (23.9%, 17 of 71), than patients with small bowel involvement alone (2.8%, 1 of 36) (P = 0.013)”. (2)
Amongst the extraintestinal manifestations of IBD, iritis and uveitis are the most common, with 2.2% of women and 1.1% of men experiencing the issues.  They are most common in ulcerative colitis sufferers, with a rate of occurrence of 3.8% in women with UC.  These are actual IBD manifestations, as opposed to co-morbid diseases like asthma.  Uveitis is an often painful inflammation of the uvea, or middle structures of the eye.  Iritis is really anterior uveitis – the iris is part of the uvea – but is sometimes tracked separately.  Uveitis can result in blurry vision, light sensitivity, and redness in the eye.  Use of entanercept (Enbrel) was associated with an largely increased chance of uveitis occurring (beyond that of IBD in general), whereas infliximab (Remicade) and adalimumab (Humira) showed no increase in uveitis.(3,4)
Episcleritis and scleritis are an inflammation of the outer, white area of the eye.  Episcleritis is less severe in general, and both are treatable.  Though occurring at a higher rate in IBD, one of the primary treatments for both is the use of Infliximab, which has been shown to have a positive anti-inflammatory effect on the conditions.(5)
One of the biggest concerns for eyes and IBD comes not from the disease but from its treatment.  Prednisone use has been shown to greatly increase the risk of developing glaucoma through an increased Intraocular Pressure (IOP).  Specifically, a portion of the population is genetically susceptible to increased IOP through the use of steroids, potentially as high as one third.  The increased IOP causes nerve damage, and can eventually lead to blindness.(6)
The eyes are an often overlooked area for IBD to manifest itself.  Anyone with Crohn’s, especially Crohn’s Colitis, or with Ulcerative Colitis should get annual eye exams from a licensed optometrist or ophthalmologist.  Additionally, because an increased IOP can have rapid and irreversible impact, any eye issues should be treated as a medical emergency and evaluated immediately by a physician.

Bottom Line

·         Eye issues affect approximately 10% of those with IBD, and up to 20% of those with colon involvement.
·         All of eye issues can progress to glaucoma and potentially blindness.  Any eye problems that manifest should be treated as a medical emergency.
·         Yearly visits to your optometrist or ophthalmologist should be considered a regular part of your preventative care regimen. 
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1.       Manganelli, C., S. Turco, and E. Balestrazzi. "Ophthalmological aspects of IBD." Eur Rev Med Pharmacol Sci 13, no. Suppl 1 (2009): 11-13.
2.       Salmon, J. F., J. P. Wright, and A. D. Murray. "Ocular inflammation in Crohn's disease." Ophthalmology 98, no. 4 (1991): 480-484.
3.       Bernstein, Charles N., James F. Blanchard, Patricia Rawsthorne, and Nancy Yu. "The prevalence of extraintestinal diseases in inflammatory bowel disease: a population-based study." The American journal of gastroenterology 96, no. 4 (2001): 1116-1122.
4.       Lim, Lyndell L., Frederick W. Fraunfelder, and James T. Rosenbaum. "Do tumor necrosis factor inhibitors cause uveitis? A registrybased study." Arthritis & Rheumatism 56, no. 10 (2007): 3248-3252.
5.       Mintz, Roni, Edward R. Feller, Robert L. Bahr, and Samir A. Shah. "Ocular manifestations of inflammatory bowel disease." Inflammatory bowel diseases10, no. 2 (2004): 135-139.

6.       Tripathi, Ramesh C., Sunil K. Parapuram, Brenda J. Tripathi, Yong Zhong, and K. V. Chalam. "Corticosteroids and glaucoma risk." Drugs & aging 15, no. 6 (1999): 439-450.

Sunday, November 10, 2013

Libations and IBD

Alcohol, Crohn's, and Ulcerative Colitis

Alcohol, more specifically ethyl alcohol (or ethanol), is a result of sugar fermentation.  Humans are believed to have consumed alcohol since prehistoric times.  Primarily a central nervous system depressant, alcohol has several sought-after psychoactive properties which have led to its recreational consumption in beverages and inclusion in recipes.  More specifically, small amounts of alcohol are found to produce short term euphoric effects, including increased self confidence and more relaxed social interactions.  In cooking, alcohol’s ability to evaporate quickly and act as a solvent for flavors that are not water-soluble are valuable assets, and the flair added to “flaming” dishes makes for dramatic presentation.

Alcohol use, like many other substances, has both positive and negative effects on those with IBD.  In general, the effects of moderate consumption of alcohol have been shown to have minimal negative and potential positive health effects.  The amount that is considered “moderate” varies per person and is a factor of gender, genetics, and size.  For an average woman, one-to-one and a half servings a day are considered moderate, whereas a large man may have two or two and a half servings at the moderate consumption level.  While most individuals with Crohn’s and Ulcerative Colitis are told to avoid alcohol, and they will self-report digestive problems after consumption, the number of individuals with IBD that drink is similar to the population at large.(1)

As a primary positive factor, a lower risk of coronary artery disease has been correlated with regular, small amounts of alcohol consumption.  With respect to IBD, moderate consumption has been shown to be correlated with lower C-Reactive Protein levels, one of the key markers associated with inflammation in the disease.(2)  Though there is a correlation, there is no direct evidence that there is a positive impact on intestinal inflammation, just systemic markers of inflammation (there is no negative impact shown either).  There is little evidence that minimum to moderate amounts of alcohol have any long-term negative effects on IBD outcomes.  In fact, consumption of smaller amounts of alcohol has been shown to have a protective effect against developing Ulcerative Colitis (odds ratio = .57).(3)

While moderate consumption has been shown to have minimal impact, higher consumption levels, both acute and chronic, have serious negative consequences.  The well-known acute impacts of consumption that are non-GI specific include impaired judgment, vomiting, slowing of cardiac function, and an altered level of consciousness (to include coma and death at the highest levels).  The effects of high level chronic consumption are additionally severe – including liver disease, coronary disease, and dependency-related issues.

While light-to-moderate consumption may show no evidence of impact on disease progression, moderate-to-heavy consumption has been shown to have an impact.  Ulcerative Colitis sufferers are more like have a relapse (Odds Ratio = 2.7) if they are in the top third of the IBD population in alcohol consumption v. the bottom third. (4) Additionally, because of intestinal permeability issues associated with IBD, there is a potential higher likelihood for co-morbid cirrhosis of the liver to develop in those who consume heavy amounts of alcohol. (5)

Despite the general rules, there are some specific circumstances where alcohol consumption is contraindicated for those with IBD.  Originally, metronidazole (Flagyl) was reported to have a deadly disulfiram-like reaction when alcohol was consumed while taking the drug.  The original reports have largely been dismissed at this point, though the possibility of multi-drug interactions still exist.(6,7)  Immunomodulators like methotrexate have an increased risk of liver damage, and alcohol consumption can increase this risk.  Additionally, drugs like Zantac and Tagamet can increase absorption leading to a higher blood alcohol level. (8)

Alcohol is not only in the things we drink – it can be in everything from cough medicines to mouth wash.  Alcohol is frequently used in cooking also – there is an unfounded assumption that alcohol burns off quickly (because of a quicker evaporation than water) .  The real story is more complicated – the smaller the pot, the less evaporates.  Additionally, the lower the temperature the less evaporates.  A table from the USDA (below) shows the evaporation for everything from flambĂ© to simmering at various cooking times (uncovered).

Technique
Percentage Alcohol
Remaining
Alcohol, overnight evaporation
70
Alcohol added to hot liquid
85
Flambé
75
Alcohol 15 minutes cooking
40
Alcohol 30 minutes cooking
35
Alcohol 1 hour cooking
25
Alcohol 1.5 hours cooking
20
Alcohol 2 hours cooking
10
Alcohol 2.5 hours cooking
5


Bottom Line


·         Light consumption of alcohol is likely to have no negative effect on Crohn’s and Ulcerative Colitis progression
·         Heavy consumption of alcohol can have a serious impact on IBD and general health
·         If you are on medications, multi-drug interactions can be exacerbated by alcohol.  Talk to your doctor and ask them to show you the research on your particular meds!
·         Alcohol can and does appear in non-drink form in cough syrups, mouthwash, and many dishes in restaurants.  Cooking does not generally remove much of the alcohol content.

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1.       Swanson, Garth R., Shahriar Sedghi, Ashkan Farhadi, and Ali Keshavarzian. "Pattern of alcohol consumption and its effect on gastrointestinal symptoms in inflammatory bowel disease." Alcohol 44, no. 3 (2010): 223-228.
2.       Albert, Michelle A., Robert J. Glynn, and Paul M. Ridker. "Alcohol consumption and plasma concentration of C-reactive protein." Circulation 107, no. 3 (2003): 443-447.
3.       Nakarnura, Yosikazu, and Darwin R. Labarthe. "A case-control study of ulcerative colitis with relation to smoking habits and alcohol consumption in Japan." American journal of epidemiology 140, no. 10 (1994): 902-911.
4.       Jowett, S. L., C. J. Seal, M. S. Pearce, E. Phillips, W. Gregory, J. R. Barton, and M. R. Welfare. "Influence of dietary factors on the clinical course of ulcerative colitis: a prospective cohort study." Gut 53, no. 10 (2004): 1479-1484.
5.       Keshavarzian, A., E. W. Holmes, M. Patel, F. Iber, J. Z. Fields, and S. Pethkar. "Leaky gut in alcoholic cirrhosis: a possible mechanism for alcohol-induced liver damage." The American journal of gastroenterology 94, no. 1 (1999): 200-207.
6.       Williams, Caroline S., and Kevin R. Woodcock. "Do ethanol and metronidazole interact to produce a disulfiram-like reaction?." The Annals of pharmacotherapy34, no. 2 (2000): 255-257.
7.       Visapaa, J. P., Jyrki S. Tillonen, Pertti S. Kaihovaara, and Mikko P. Salaspuro. "Lack of disulfiram-like reaction with metronidazole and ethanol." The Annals of pharmacotherapy 36, no. 6 (2002): 971-974.

Sunday, November 3, 2013

Zeitgeist of IBD

IBD Terms Over Time

The evolution of inflammatory bowel disease can be tracked using Google’s ngram viewer.  In addition to providing the frequency of words and phrases appearing in books, the viewer can be used to identify trends and the uptake of new concepts in the literature (which largely mirrors practice).  The medical establishment has always been one of the more vivacious adopters of the written word for disseminating their ideas, and the evolution of inflammatory bowel disease is no exception.

Aside from IBD, there are general, positive trends in medicine that can be extracted.  Look at the difference between the terms “Case History” and “Clinical Trial”, and you can see the positive movement toward evidence-based medicine.  While the trend was present, the term “evidence based medicine” didn’t really take off until the 1990s, but is showing a growing popularity.


This blog is called “Evidence Based IBD”, but the term inflammatory bowel disease is relatively new.  Originally, the term “Regional Enteritis” was the used for both ulcerative colitis and Crohn’s Disease, but has fallen out of favor.  Dr. Crohn’s description occurred in the 1932, but the linking of the disease to his name didn’t really take off until the 1960’s,  whereas ulcerative colitis was well known in the 1800’s. 


The treatments for Crohn’s and IBD are similarly mapped to their dates of identification and their dates of greatest usage.  As new treatments arise, older treatments become less prominent in the literature.  Some of this is due to the treatments falling out of favor, but some of it is simply due to a lack of interest in new clinical trials proving already proven treatments (though they still frequently appear as comparisons to new modalities).  The decline in prednisone, methotrexate, and aminosalicylic acid (5-ASA) against the growth of the anti-TNF agents can be shown below.


Similar to the above, the use of terms can signify their relative importance within a class.  Generally, the first arriver ends up being the most cited (for an extended period).  This can be seen by comparing Remicade (infliximab) to Humira (adalimumab) and Cimzia (not approved until 2008).



The basic ngram analysis is fun, and Google can be used to show large trends, but too much should not be read into the results.  That said, it is an interesting respite from some of the more detailed recent blog postings.


Bottom Line



·         Google ngram analysis is a fun research tool that shows the changes in the wording around IBD and can be used as a basic popularity tool over time.