What is Extraintestinal Manifestations of Inflammatory Bowel Disease?
Inflammatory bowel disease (IBD) is a long-term disorder triggered by the immune system, which includes Crohn’s disease and ulcerative colitis. Ulcerative colitis impacts the large intestine, while Crohn’s disease can affect any part of the digestive tract. IBD predominantly affects the digestive system, bones and muscles, eyes, and skin. However, complications that arise elsewhere in the body are referred to as extraintestinal manifestations (EIMs). These EIMs can actually cause more health problems for IBD patients than the intestinal disease itself, and they can occur in up to 50% of all IBD patients.
The frequency and severity of these EIMs and their connection to intestinal IBD can vary. Many are directly linked to active intestinal flare-ups such as mouth ulcers, certain types of arthritis, skin inflammation, and eye inflammation. Other EIMs like a specific type of arthritis known as ankylosing spondylitis and eye inflammation known as uveitis can occur regardless of intestinal disease activity. EIMs can appear before, during, or after IBD is diagnosed. Research has shown that if a patient develops one EIM, they are more likely to develop additional EIMs.
The most common symptoms unrelated to the intestines in IBD patients manifest in the musculoskeletal system, occurring in about 40% of IBD patients. This can take the form of arthritis or inflammation of various joints or parts of the spine. Skin symptoms occur in up to 15% of IBD patients, with issues like painful red or purple nodules on the legs, skin ulcers, or mouth ulcers. Treatment typically involves elevating the legs, wearing compression socks, and using pain and anti-inflammatory medications.
About 2% to 5% of IBD patients have eye-related symptoms, making eyes the third most common area affected by IBD, following joints and skin. The most common eye issues include inflammation of various parts of the eye. These conditions can lead to feelings of burning, irritation, pain, redness, or even vision impairment in severe cases. It’s crucial to promptly treat these conditions to prevent long-term vision loss.
Half of IBD patients will develop liver-related complications at some point during their illness. Various manifestations include inflammation and hardening of bile ducts, liver inflammation, fatty liver disease, poor bile flow, gallstones, and pancreatitis. These symptoms are independent of intestinal-IBD activity, and hence treating IBD does not necessarily improve these conditions. Treatments often include medication, specific medical procedures, or even liver transplants.
Other complications of IBD can include kidney stones due to malabsorption in the intestine, increased risk of blood clots unrelated to intestinal disease activity, and problems with bone health leading to low bone mass and fractures. Some patients may also develop lung and kidney diseases, but the prevalence is uncertain.
What Causes Extraintestinal Manifestations of Inflammatory Bowel Disease?
Inflammatory bowel disease (IBD) and its extra-intestinal manifestations (EIMs) have multiple causes that include genetic factors, issues with the immune system, and changes in the gut bacteria balance. This contributes to prolonged inflammation in the body, which leads to the symptoms of the disease. It’s believed that EIMs happen because of an abnormal immune response to shared characteristics in the gut lining and the disease areas outside the intestines.
EIMs also have a genetic predisposition. Meaning, if you have family members, particularly siblings or parents, with IBD, you are more likely to develop these symptoms as well. Certain genetic characteristics, known as major histocompatibility complex loci, are linked to IBD and its EIMs. For example, in Crohn’s disease, HLA-A2, HLA-DR1, and HLA-DQw5 are connected to EIMs. Meanwhile, in ulcerative colitis, HLA-DR103 is linked to EIMs. Specific EIMs are also associated with certain HLA complexes.
Some research suggests that EIMs might develop as an autoimmune response towards a specific protein found in different parts of the body including the eye, skin, joints, liver, and bile ducts, and the gut lining. Animal studies have shown that changes in the normal gut bacteria can lead to intestinal inflammation seen in IBD. However, understanding whether or not this applies to humans is still being researched.
Risk Factors and Frequency for Extraintestinal Manifestations of Inflammatory Bowel Disease
Extraintestinal manifestations (EIMs), which are complications affecting parts of the body outside the intestines, can occur in people with Inflammatory Bowel Disease (IBD). These complications can impact between 5% and 50% of IBD patients at least once in their lifetime. Around 31% of IBD patients with Crohn’s disease and 43% of those with ulcerative colitis might experience EIMs. It’s also more common in females (50%) than in males (34%). However, children seem to experience these complications less frequently than adults.
- At least one EIM might impact about 63% of IBD patients in their lifetime.
- Two EIMs might be reported in around 27% of IBD patients.
- Among all the types of EIMs, arthritis is the most common, followed by oral aphthous ulcers (painful sores in the mouth) and uveitis (eye inflammation).
Signs and Symptoms of Extraintestinal Manifestations of Inflammatory Bowel Disease
People with Inflammatory Bowel Disease (IBD), need complete assessments when they visit the clinic. It’s important to check for symptoms that affect other parts of the body, in addition to the gastrointestinal symptoms. Common symptoms patients report include stomachache and bloating, changes in bowel habits like diarrhea or constipation, fatigue, loss of weight, discomfort in the anus (tenesmus), and inflammation in joints, skin, eyes, and liver. Also, a detailed family history is crucial because if a family member has IBD, it increases the chance of having the disease too.
- Stomachache and bloating
- Diarrhea or constipation
- Fever
- Fatigue
- Weight loss
- Discomfort in the anus (tenesmus)
- Inflammation in joints, skin, eyes, and liver
Testing for Extraintestinal Manifestations of Inflammatory Bowel Disease
To correctly diagnose and manage inflammatory bowel disease (IBD) and its associated conditions, a careful evaluation is essential. This process includes taking a detailed medical history, performing a thorough physical check-up, followed by the right lab tests and imaging procedures.
Stool analysis and blood tests are among the routinely used lab tests. As for the imaging procedures, they can range from X-rays and CT scans (computed tomography scans) to MRI (magnetic resonance imaging). In some cases, capsule endoscopy, flexible colonoscopy, or sigmoidoscopy may be used to get a detailed look at the patient’s intestinal health. These tests and procedures help provide a more concrete diagnosis and enable effective treatment of IBD and its related conditions.
Treatment Options for Extraintestinal Manifestations of Inflammatory Bowel Disease
Treating extraintestinal manifestations (EIMs) of inflammatory bowel disease (IBD) often involves a combined approach of lifestyle changes and medications. Generally, managing IBD itself often results in the resolution of EIMs that are linked with the disease activity.
The initial step in mild IBD treatment is reducing inflammation using anti-inflammatory medications such as corticosteroids and aminosalicylates. If these are ineffective due to moderate disease activity, immunosuppressant drugs such as methotrexate, azathioprine, and mercaptopurine are prescribed to suppress the immune system and calm the inflammation that affects various tissues in IBD.
If IBD is severe, newer drug treatments called biological agents, like anti-tumor necrosis factor agents, are employed. Antibiotics like metronidazole and ciprofloxacin are used to handle secondary infections that can come with IBD. Other treatments can include vitamin supplements, medications to control diarrhea, and pain relievers to help manage symptoms.
EIMs that don’t relate directly to IBD activity require specific treatment to enhance quality of life and reduce illness and death rates. Physical therapy, pain medication, and anti-inflammatory drugs like nonsteroidal anti-inflammatory drugs and systemic corticosteroids are used to manage musculoskeletal EIMs of IBD. Skin issues like pyoderma gangrenosum need topical steroid therapy alongside wound care. Eye issues, such as scleritis and uveitis, are treated with topical steroids.
Currently, no treatment can cure primary sclerosing cholangitis (PSC), an EIM of IBD, so those with a progressive disease course might eventually need a liver transplant.
Lifestyle changes such as quitting smoking, keeping active, staying well-hydrated, managing stress, and avoiding dairy products can improve IBD symptoms. As IBD is a long-term disease with physical and mental effects, patients are encouraged to join support groups and seek therapy. They should also have routine colonoscopies due to the risk of colon cancer associated with IBD.
What else can Extraintestinal Manifestations of Inflammatory Bowel Disease be?
It’s important to distinguish between conditions related directly to Inflammatory Bowel Disease (IBD), and those caused by chronic illness, poor nutrition, or treatment side effects. IBD often affects areas outside the intestines. For example, joint problems are quite common.
However, some symptoms might resemble these effects but are actually side effects from the medications used to treat IBD. For instance, corticosteroids, a common IBD treatment, could cause bone death, known as osteonecrosis. Another treatment, the anti-tumor necrosis factor, might result in a form of arthritis known as lupus arthropathy.
It’s also crucial to consider other health issues that have symptoms similar to IBD. These can include celiac disease, difficulty digesting lactose, ulcers in the stomach or intestines, Irritable Bowel Syndrome (IBS), common infections such as traveler’s diarrhea or gastroenteritis, and even colorectal cancer.
What to expect with Extraintestinal Manifestations of Inflammatory Bowel Disease
Inflammatory Bowel Disease (IBD) usually follows a pattern of flaring up and then improving. Despite this, most patients can still lead active and healthy lives. Taking the right medication and making changes to lifestyle can help control the symptoms of IBD.
Keeping a keen eye on any symptoms and managing them early on can make a big difference in the patient’s health and their quality of life, as well as reduce the risk of further health problems. There are certain symptoms linked with the activity of IBD that show up during flare-ups. On the other hand, some symptoms aren’t related to how severe the IBD is, and these may be noticed before an IBD diagnosis or during times when the disease is in remission.
Possible Complications When Diagnosed with Extraintestinal Manifestations of Inflammatory Bowel Disease
Inflammatory bowel disease (IBD) is a complex condition that can cause a number of serious problems. The issue of not absorbing nutrients properly and losing blood over time can result in a lack of iron and essential vitamins. This can lead to anemia, a condition where your body doesn’t have enough red blood cells. Inflammation in the intestines might also cause strictures (narrowings) and fistulas (abnormal connections between different parts of your body). These issues are usually seen in people with Crohn’s disease, a type of IBD.
The most common kind of fistula occurs near the anus, but it can also happen between the intestines, from the intestines to the skin, between the intestines and bladder, or between the intestines and vagina. Another type of IBD, ulcerative colitis, raises your risk of having a dangerously enlarged colon, a punctured colon, and colon cancer. If not treated, Primary Sclerosing Cholangitis (PSC), a condition that causes inflammation and scarring of the bile ducts, may progress to a severe level, causing liver cirrhosis and failure.
Chronic inflammation can make your blood more likely to clot, which can lead to deep vein thrombosis (blood clots in deep veins) and pulmonary embolism (blocked artery in the lungs). Chronic inflammation, malnutrition, and treatment therapies can also lead to weakened and brittle bones, failure to grow, amyloidosis (a build-up of abnormal proteins), and fatty liver disease.
Here are the potential complications of IBD:
- Iron deficiency anemia and vitamins deficiency anemias due to malabsorption and blood loss
- Fistulas and strictures due to constant inflammation in the intestine
- Perianal, entero-enteric, entero-cutaneous, entero-vesical, or entero-vaginal fistulas
- Risks of toxic megacolon, colon puncture, and colon cancer linked with ulcerative colitis
- Potential for liver cirrhosis and hepatic failure if Primary Sclerosing Cholangitis (PSC) is untreated
- Chances of deep vein thrombosis and pulmonary embolism due to a hypercoagulable state from chronic inflammation
- Possibility of weakened bones, growth failure, amyloidosis, and fatty liver disease due to chronic inflammation, malnutrition, and treatment therapies
Preventing Extraintestinal Manifestations of Inflammatory Bowel Disease
Inflammatory Bowel Disease (IBD) can lead to various issues that extend beyond the intestines. These can include problems like nutritional deficiencies, reduced bone density (osteopenia and osteoporosis), and the development of kidney and gall stones. It may also cause problems with the nerves in your arms and legs (peripheral neuropathies), or side effects from IBD medications. It’s essential to be careful when taking drugs like Nonsteroidal anti-inflammatory drugs that manage IBD-related symptoms outside the gut, as these can sometimes make IBD worse.
As IBD can increase the risk of bone loss and low levels of calcium (hypocalcemia), doctors should advise patients about the benefits of quitting smoking, exercising regularly, and including calcium and vitamin D in their diet. People with IBD may also be at a higher risk of blood clots during long periods of immobility, such as during long flights. Preventive measures would include staying well-hydrated, avoiding smoking, exercising regularly, and wearing compression stockings where appropriate.
