ulcerative colitis

Posted on Gastrointestinal disorders

Multi-population risk scores could improve risk prediction for inflammatory bowel diseases, study finds

Using genetic data from nearly 30,000 people, Mount Sinai researchers have built risk scores from a combination of datasets representing distinct ancestral populations that improve prediction of risk for inflammatory bowel diseases (IBD) including Crohn’s disease and ulcerative colitis. The study was published in Gastroenterology on December 24.

The researchers found that polygenic risk scores, built using association data from multiple populations in Mount Sinai’s multi-ethnic BioMe Biobank, maximized IBD predictions for every population in the biobank. BioMe is a system-wide effort at Mount Sinai that is revolutionizing diagnosis and classification of diseases according to the patient’s molecular profile. The study showed that risk scores calculated from integrating data significantly improved predictions among individuals with European, Ashkenazi Jewish, and Hispanic ancestry in BioMe, as well as European individuals in the UK Biobank, which contains biological and medical data on half a million people between ages 40 and 69 living in the UK. Predictive power was lower for patients with African ancestry, likely due to substantially smaller reference datasets and substantially greater genetic diversity within populations of African descent.

“The ability to accurately predict genetic disease risk in individuals across ancestries is a critical avenue that may positively affect patient outcomes, as early interventions and even preventive measures are being considered and developed,” says the study’s senior author Judy H. Cho, MD, Dean of Translational Genetics and Director of The Charles Bronfman Institute for Personalized Medicine at the Icahn School of Medicine at Mount Sinai. “These findings support a need for greater genetic diversity, including more data on African American populations, to enhance disease risk predictions and reduce health disparities for all populations.”

These polygenic risk scores–representing an estimate of overall risk based on the sum of an individual’s many, mostly common, genetic variants–were calculated using IBD association data from cohorts with European, African American, and Ashkenazi Jewish backgrounds. Additionally, researchers assessed rare variants in genes associated with very-early-onset IBD within each population and found that African American carriers of uncommon LRBA variants showed reduced expression of both proteins LRBA and CTLA-4. LRBA deficiency increases susceptibility to IBD and results in lower CTLA-4 expression, which can be reversed with the commonly prescribed antimalarial drug chloroquine. Future studies by the Cho Laboratory will focus on predicting which subsets of patients might benefit from targeting this pathway.

“Since lowered LRBA and CTLA-4 expression can lead to IBD, it’s encouraging that chloroquine is able to partially recover expression,” says the study’s first author Kyle Gettler, PhD, postdoctoral fellow in the Department of Genetics and Genomic Sciences at the Icahn School of Medicine at Mount Sinai.

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Ulcerative Colitis – what are the signs and symptoms of Ulcerative Colitis?




Ulcerative Colitis - what are the signs and symptoms of Ulcerative Colitis?

Ulcerative Colitis – what are the signs and symptoms of Ulcerative Colitis?

Ulcerative Colitis

Ulcerative colitis is a long-term condition, where the colon and rectum become inflamed.




The colon is the large intestine (bowel), and the rectum is the end of the bowel where stools are stored.

Small ulcers can develop on the colon’s lining, and can bleed and produce pus.

Symptoms of ulcerative colitis

The main symptoms of ulcerative colitis are:

recurring diarrhoea, which may contain blood, mucus or pus

abdominal (tummy) pain

needing to empty your bowels frequently

You may also experience fatigue (extreme tiredness), loss of appetite and weight loss.

The severity of the symptoms varies, depending on how much of the rectum and colon is inflamed and how severe the inflammation is. For some people, the condition has a significant impact on their everyday lives.

Symptoms of a flare-up

Some people may go for weeks or months with very mild symptoms, or none at all (known as remission), followed by periods where the symptoms are particularly troublesome (known as flare-ups or relapses).

During a flare-up, some people with ulcerative colitis also experience symptoms elsewhere in their body. For example, some people develop:

painful and swollen joints (arthritis)

mouth ulcers

areas of painful, red and swollen skin

irritated and red eyes

In severe cases, defined as having to empty your bowels six or more times a day, additional symptoms may include:

shortness of breath

a fast or irregular heartbeat

a high temperature (fever)

blood in your stools becoming more obvious

In most people, no specific trigger for flare-ups is identified, although a gut infection can occasionally be the cause. Stress is also thought to be a potential factor.




Read more about living with ulcerative colitis.

When to seek medical advice

You should see your GP as soon as possible if you have symptoms of ulcerative colitis and you haven’t been diagnosed with the condition.

They can arrange blood or stool sample tests to help determine what may be causing your symptoms. If necessary, they can refer you to hospital for further tests.

Read more about diagnosing ulcerative colitis.

If you’ve been diagnosed with ulcerative colitis and think you may be having a severe flare-up, contact your GP or care team for advice. You may need to be admitted to hospital.

 

What causes ulcerative colitis?

Ulcerative colitis is thought to be an autoimmune condition. This means the immune system – the body’s defence against infection – goes wrong and attacks healthy tissue.

The most popular theory is that the immune system mistakes harmless bacteria inside the colon for a threat and attacks the tissues of the colon, causing it to become inflamed.

Exactly what causes the immune system to behave in this way is unclear. Most experts think it’s a combination of genetic and environmental factors.

 

Who’s affected?

It’s estimated that around 1 in every 420 people living in the UK has ulcerative colitis; this amounts to around 146,000 people.

The condition can develop at any age, but is most often diagnosed in people from 15 to 25 years old.

It’s more common in white people of European descent (especially those descended from Ashkenazi Jewish communities) and black people. The condition is rarer in people from Asian backgrounds (although the reasons for this are unclear).

Both men and women seem to be equally affected by ulcerative colitis.

How ulcerative colitis is treated

Treatment for ulcerative colitis aims to relieve symptoms during a flare-up and prevent symptoms from returning (known as maintaining remission).

In most people, this is achieved by taking medication such as:

Mild to moderate flare-ups can usually be treated at home. However, more severe flare-ups need to be treated in hospital to reduce the risk of serious complications, such as the colon becoming stretched and enlarged or developing large ulcers. Both of these can increase the risk of developing a hole in the bowel.

If medications aren’t effective at controlling your symptoms, or your quality of life is significantly affected by your condition, surgery to remove your colon may be an option.

During surgery, your small intestine will either be diverted out of an opening in your abdomen (known as an ileostomy), or used to create an internal pouch that’s connected to your anus (known as an ileo-anal pouch).

 

Anus
The anus is the opening at the end of the digestive system where solid waste leaves the body.
Chronic
Chronic usually means a condition that continues for a long time or keeps coming back.
Disease
A disease is an illness or condition that interferes with normal body functions.
Genetic
Genetic is a term that refers to genes- the characteristics inherited from a family member.
Inflammation
Inflammation is the body’s response to infection, irritation or injury, which causes redness, swelling, pain and sometimes a feeling of heat in the affected area.
Pain
Pain is an unpleasant physical or emotional feeling that your body produces as a warning sign that it has been damaged.
Remission
Remission is when the symptoms of a condition are reduced (partial remission) or go away completely (complete remission).
Stools
Stool (also known as faeces) is the solid waste matter that is passed from the body as a bowel movement.
Ulcers
An ulcer is a sore break in the skin, or on the inside lining of the body.
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Abdominal pain – what are the signs, symptoms, cause and treatments of a stomach ache




A stomach ache is a term often used to refer to cramps or a dull ache in the tummy (abdomen). It’s usually short-lived and is often not serious.

Stomach ache and abdominal pain - your guide

Stomach ache and abdominal pain – your guide

Severe abdominal pain is a greater cause for concern. If it starts suddenly and unexpectedly, it should be regarded as a medical emergency, especially if the pain is concentrated in a particular area.




Call your GP as soon as possible or go to your nearest hospital accident and emergency (A&E) department if this is the case.

If you feel pain in the area around your ribs, read about chest pain for information and advice.

Stomach cramps with bloating

Stomach cramps with bloating are often caused by trapped wind. This is a very common problem that can be embarrassing, but is easily dealt with. Your chemist will be able to recommend a product which can be bought over the counter to treat the problem.

Sudden stomach cramps with diarrhoea

If your stomach cramps have started recently and you also have diarrhoea, the cause may be a tummy bug (gastroenteritis). This means you have a viral or bacterial infection of the stomach and bowel, which should get better without treatment after a few days.

Gastroenteritis may be caused by coming into close contact with someone who’s infected, or by eating contaminated food (food poisoning).




If you have repeated bouts of stomach cramps and diarrhoea, you may have a long-term condition, such as irritable bowel syndrome.

Sudden severe abdominal pain

If you have sudden agonising pain in a particular area of your tummy, call your GP immediately or go to your nearest A&E department. It may be a sign of a serious problem that could rapidly get worse without treatment.

Serious causes of sudden severe abdominal pain include:

appendicitis – the swelling of the appendix (a finger-like pouch connected to the large intestine), which causes agonising pain in the lower right-hand side of your abdomen, and means your appendix will need to be removed
a bleeding or perforated stomach ulcer – a bleeding, open sore in the lining of your stomach or duodenum (the first part of the small intestine)
acute cholecystitis – inflammation of the gallbladder, which is often caused by gallstones; in many cases, your gallbladder will need to be removed
kidney stones – small stones may be passed out in your urine, but larger stones may block the kidney tubes, and you’ll need to go to hospital to have them broken up
diverticulitis – inflammation of the small pouches in the bowel that sometimes requires treatment with antibiotics in hospital

If your GP suspects you have one of these conditions, they may refer you to hospital immediately.

Sudden and severe pain in your abdomen can also sometimes be caused by an infection of the stomach and bowel (gastroenteritis). It may also be caused by a pulled muscle in your abdomen or by an injury.

Long-term or recurring abdominal pain

See your GP if you or your child have persistent or repeated abdominal pain. The cause is often not serious and can be managed.

Possible causes in adults include:

irritable bowel syndrome (IBS) – a common condition that causes bouts of stomach cramps, bloating, diarrhoea or constipation; the pain is often relieved when you go to the toilet
inflammatory bowel disease (IBD) – long-term conditions that involve inflammation of the gut, including Crohn’s disease and ulcerative colitis
a urinary tract infection that keeps returning – in these cases, you will usually also experience a burning sensation when you urinate
constipation
period pain – painful muscle cramps in women that are linked to the menstrual cycle
other stomach-related problems – such as a stomach ulcer, heartburn and acid reflux, or gastritis (inflammation of the stomach lining)

Possible causes in children include:

constipation
a urinary tract infection that keeps returning
heartburn and acid reflux
abdominal migraines – recurrent episodes of abdominal pain with no identifiable cause

 

[Original article on NHS Choices website]

1 Comment Posted on Patient Talk

Ulcerative Colitis – what it is and how to treat ulcerative colitis!


Professor Chris Probert

Professor Chris Probert

New research findings this week show that people with ulcerative colitis (UC) who have had surgery to remove their colon continue to experience UC symptoms, with around three-quarters of patients saying the biggest impacts of the disease are on their emotional state (in terms of depression, anger or anxiety levels) and ability to rest/sleep.

We interviewed to find out more about ulcerative colitis and the treatments avaiable for ulcerative colitis.


PATIENTTALK.ORG -I’m here with Professor Chris Probert, Gastroenterologist of Royal Liverpool Hospital and today we are talking about some new research findings which show that 4 out of 5 people with ulcerative colitis who have had surgery to remove their colon continue to experience symptoms, with around 3 quarter of patients saying the biggest impacts of the disease are on their emotional state. So professor Probert I was wondering if you could please just explain a little bit of about what ulcerative Colitis is and how it differs from Crohn’s disease.

PROF PROBERT – Thank you , ulcerative Colitis is an inflammatory condition affecting the large bowl colon ,and when the colon is inflamed, the patient will experience diarrhoea, cramping and often will bled. Crohn’s disease is a different condition although it’s a bowl inflamed, the small bowl and the large bowl are inflamed in some patients and the disease is quite patchy, so some patients with Crohn’s disease it will just be a small segment of the small bowel, small segment of the large bowl or it can be all over so they are quite different in the distribution and the treatment options are different as well.

PATIENTTALK.ORG -So speaking about distribution, how common is this and how many people are affected by this?

PROF PROBERT – In the UK we think there are about 150 thousand patients with ulcerative Colitis.

PATIENTTALK.ORG -So could you please just run through the early sings of and symptoms that someone would experience if they had ulcerative Colitis undiagnosed?

PROF PROBERT – Patients with ulcerative Colitis will experience initially typically diarrhoea and they will realise this has not gone away the same way as it would with a bug and after a week or two they are starting to start feeling unwell and maybe notice some bleeding, Some patients it can settle down a little bit and then return later, for others it just escalates and it can go from perfect health to life threatening Colitis within a matter of weeks. So there’s a spectrum of ways in which patients present from mild through to moderate.

PATIENTTALK.ORG -Its mentioned in the research that some patients are experiencing a flare up, how often does this lead to hospitalisation?

PROF PROBERT – Patients who have a flare up are the ones who have diarrhoea and bleeding and between the flares hopefully patients are feeling relatively well without too many symptoms. During a flare up if the patient is going to the toilet more then 6 -8 times a day then they should definitely be considered by a specialist to go into hospital, if the patient is feverish then they will clearly need to be in hospital having intravenous therapy as that is a very serious situation potential life threatening situation . Overall about 1 in 10 patients will have a severe flare up at any time.

PATIENTTALK.ORG -So if you’re diagnosed with ulcerative Colitis what sort of life style changes are to be expected and what sort of impact does this have on the people you work with?

PROF PROBERT – Ulcerative Colitis can have a very big impact om patients life’s, if they are lucky enough to have a mild disease it’s a matter of taking the right medication, being a little bit wary , not exposing yourself to the risk of food poisoning and so forth. Patients with a more moderate disease this is starting to get a bit more serious, the treatment will be taken more frequently, they are likely to have steroids more often, they have steroids side effects and that can make you very moody, gain weight and make you feel quite groggy. And for those patients they start to feel rather edgy and insecure you know they don’t know whether the next time they are going to have diarrhoea, they are constantly on the lookout for lavatories and with a country with poor public loos that is a problem, patients know every lavatory between home and school or home and their work place, it makes you very very insecure, it knocks your confidence and constant fatigue.

PATIENTTALK.ORG -Ok so just running through the findings a little bit, the research was done by merk showman limited and what they found was only a third of patients are completely satisfied with their current treatment. So this obviously has something to do with the findings that 4 out of 5 people who have the surgery to have their colon removed are still experiencing the symptoms, so what sort of other options are there? It says here that Nice the medical recommendation of the NHS the body is looking at issuing some guidance on medical options of treatment, would you like to talk about that for a minute?

PROF PROBERT – So patients dissatisfied with therapy we are aware that certain treatments don’t work for everybody and some, despite our best efforts, with conventional therapy will have ongoing symptoms and require repeated courses of surgery, those patients who aren’t settling we need to think about another strategy. For many patients there is a second line group of treatments or surgery, now our concern is that there is a group off treatments that aren’t considered often enough and which at the moment NICE is reviewing, these are the biologic treatments, for patients with disease that’s not settling on conventional therapy a sub group of those will clearly respond to a the biological therapies it will turn the disease off, will prevent surgery in that group of patients, it’s not for everyone but for some patients the biologics will be life transforming. NICE at the moment are saying that this is not a treatment that they are going to support, it’s up for consultation and the consultation closes next Wednesday and we will be very interest if the patients or their relatives who has got an interest in Colitis take the opportunity of going to the NICE website or going to the Crohn’s and Colitis website and making their comments on whether they think this is a good decision. So if NICE say ‘No’ there will be more patients having surgery, if NICE say ‘yes we can use these treatments’ then that small group of patient who needs the treatments we can save an operation.

PATIENTTALK.ORG   Can you compare the situation in the UK for treatment purpose with Europe or America? Is there more common use of a medical option in Europe or is the situation broadly similar?

PROF PROBERT – Europe is big place and there is some variation country to country and it depends a lot on what we would call reinvestments and who’s going to pay for the biologic treatments and if the funder is able to support the drug, patients having them results you have heard. North America, the threshold for giving these treatments is substantially lower than in Europe and access to biologic seems a lot easier.

PATIENTTALK.ORG -So it’s in common use in USA?

PROF PROBERT – It is yes

PATIENTTALK.ORG -So is this something that NICE takes into account? Do they look at it being played out in other countries?

PROF PROBERT – No sadly they don’t, NICE have got a very strict way of looking at the world they see how many patients you can treat to get one patient healthy , how much would it cost to teat that community of patients to get that one person healthy, so the cost for an individual may not sound too much but because you have to treat a few more patients who don’t respond, the package of care seems  to be rather expensive and so by their estimates it seems to be the package of care costs more than 30 thousand pounds they are going to turn that treatment down and because there are some non-responders to the treatments the cost therefore appears to be higher than that and they are saying no at the moment to everyone , what we would like to purpose is that select out the patients who need it , who are responding to it and you only know perhaps when giving them the treatment for a few weeks couple of cycles), carry on treating those patients who are responding, don’t treat the ones who aren’t responding and that would change the hole dynamic and will change the cost of these treatments to something that might  seem acceptable to NICE but at the moment it comes down to economics.

PATIENTTALK.ORG -So anyone who’s interested in this final guidance, you did mention when this would be issued, what was the date for that?

PROF PROBERT – The way to get information on this is to go to the Cohn’s and Colitis website, they have a link to the NICE guidance and you can have a read the full documentation and anyone can upload their comments on the NICE website and consultation closes at 5pm next Wednesday, so anybody listening with Colitis or have got relatives with Colitis who thinks this is important to them should be going to the NICE website, read the documents, make your own mind up and then post your comments.