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Extra-Intestinal Manifestations of IBD

Extraintestinal Manifestations of IBD

Due to the intricate web of communication between the gut and nearly all physiological systems, and the systemic nature of IBD inflammation, symptoms can often extend beyond the gut. These symptoms are called extraintestinal manifestations (EIMs), and they can affect the health of your eyes, skin, bones, liver, kidney, and nervous system. 

Although EIMs can greatly impact the quality of life, many do resolve upon the successful management of the disease. But for those still on the road to recovery, it may help to gain a more thorough understanding of potential EIMs, and how they can be managed. 

Arthritis in IBD 

Arthritis is the most common extraintestinal manifestation of IBD, with roughly 30% of patients suffering from rheumatologic complications. 

Arthritis is the term for inflammation in the joints, which can cause pain, swelling, and a loss of flexibility. Generally, arthritis sets in with aging, but young patients with IBD often experience joint-related symptoms – even before the intestinal symptoms of IBD emerge. 

IBD-related arthritis slightly differs from common rheumatoid arthritis, which damages the joints over time. IBD-related arthritis reflects the level of colon inflammation, usually does not permanently damage the joints, and generally resolves upon the management of the underlying IBD. 

Symptoms of Arthritis include: 

  • Joint pain, aching, burning, or tenderness. 
  • Swelling and stiffness of the affected area 
  • Reduced range of motion

If your joint discomfort and stiffness is worse in the morning or after rest, it is more likely to stem from the inflammatory condition. If your joints are worse after or during physical activity, it is more likely driven by the common wear and tear that comes with use and age. 

Common Types of Arthritis in IBD

Peripheral Arthritis is the most common form of arthritis linked to IBD. This condition impacts the large joints of the legs, arms, and hips, with discomfort migrating from one joint to another. The inflammation in the joints generally reflects the level of colon inflammation. Fortunately, this type of arthritis does not cause permanent damage and typically resolves upon management of the underlying IBD. 

Axial Arthritis (also known as spondylitis or spondyloarthropathy) causes pain and stiffness in the lower spine and sacroiliac joints, which connect the pelvis to the spine. Unlike other forms of IBD-related arthritis, axial arthritis can cause permanent damage if the vertebral column bones fuse, causing restricted movement of the back, and may require biologic therapy as well as exercises to improve the range of motion. 

Ankylosing Spondylitis is a less frequent complication seen more often in Crohn’s disease than in UC. The condition affects the spine and sacroiliac joints, with inflammation also spreading to the lungs, heart valves, and eyes. Those under 30, especially young men, are most at risk. If you suspect this condition, it’s vital to see a rheumatologist as soon as possible to avoid further complications and joint damage. 

Underlying Causes of Arthritis in IBD 

While there is plenty of evidence showing a clinical relationship between gut and joint inflammation, researchers have not yet confirmed the exact mechanisms involved. 

One theory is that gut bacteria play a role in the origin of joint inflammation. Another theory is that joint inflammation in IBD may be due to the movement of intestinal lymphocytes (immune cells that normally reside between the cells that form the intestinal mucosal barrier) into the articular synovium, which is the membrane lining the joints. 

Although neither theory has been confirmed, the mirroring nature of most IBD-related joint inflammation and gut inflammation does suggest a sort of ‘gut-joint’ axis of communication.

Natural & Herbal Treatments of IBD-related Arthritis 

For those seeking a natural approach to treating arthritis, there are several herbal compounds with anti-inflammatory properties that may ease mild symptoms. 

Curcumin for Joint Inflammation 

Curcumin is an especially promising natural treatment for arthritis due to its potent anti-inflammatory properties and its ability to modulate immune system activity

In 2016, a systematic review of studies on curcumin for “joint arthritis” found that curcumin can treat arthritis. A later review in 2021 found curcumin to be a safe and effective therapy for RA (rheumatoid arthritis), helping ease morning stiffness and joint swelling. 

The benefits of curcumin for arthritis are believed to be due to its ability to suppress certain pathways and cytokines involved in the development of arthritis, including IL-17, IL-18, and RANK ligand (RANKL). RANKL is the receptor activator of the NF-κB pathway, which plays an important role in the inflammatory response. Curcumin has also been found in numerous clinical trials to suppress or inhibit IL-1, IL-17, IL-18, and dysregulated NF-kB signaling

Boswellia for Joint Inflammation 

The Arthritis Foundation recommends Boswellic acid as a treatment for rheumatoid arthritis and osteoarthritis. 

This is because Boswellia resin contains two active anti-inflammatory compounds, incensole acetate and incensole. These compounds have been shown to inhibit pro-inflammatory pathways and cytokines that drive inflammation and tissue damage in rheumatoid arthritis.

Curcumin & Boswellia for Arthritis: Better Together 

A 2018 trial recent trial tested a combined formula of Boswellic acid and curcumin on patients with osteoarthritis, which a wear-and-tear form of arthritis different from the one in IBD. Twelve weeks in, the patients reported reduced symptoms, showing that the combination treatment increased efficacy suggesting a synergist effect between the two compounds. 

Skin Conditions in IBD 

Gastrointestinal disorders such as IBD are associated with certain skin diseases, due to the bidirectional relationship between the skin and gut microbiomes and the effects of systemic immune modulation. 

Psoriasis 

IBD can, in some cases, lead to psoriasis, a skin disorder that is classified as an immune-mediated disease, meaning it is characterized by inflammation due to immune system dysfunction. 

Essentially, an overactive immune response can speed up skin cell growth, causing a buildup of unshed skin cells piled up on the surface. Researchers believe that gut dysbiosis (an imbalance of healthy and pathogenic gut bacteria) is a possible trigger for psoriasis flares. However, it is also possible that higher rate of psoriasis in IBD patients is merely a reflection of a higher risk to develop an auto-immune disease (psoriasis) in an individual with already another immune disorder (IBD)

These patches can be itchy and sore, in some cases causing the skin around the joints to crack and bleed. 

Natural Treatment for Psoriasis

The most common treatment for psoriasis is the application of topical creams or ointments onto the affected patches of skin. Emollients on the area may also help ease itching and help keep the skin moisturized and protected. 

For more severe cases, steroid creams, Vitamin D Analogue, or other non-natural medications including immunomodulators and biologics may be required to reduce the inflammation and slow down skin cell production. 

Aloe Vera for Psoriasis 

Topical use of aloe vera creams for psoriasis has shown promising results in clinical trials. Although there isn’t adequate evidence that this treatment will definitely work for psoriasis, aloe vera cream is low-risk and may provide relief due its generally soothing effect on the skin. 

The National Psoriasis Foundation recommends creams containing up to 0.5% aloe vera, which can be applied up to 3 times a day. 

Erythema Nodosum in IBD 

Erythema Nodosum (EN) is the most common skin condition associated with IBD, affecting 3-10% of UC patients and 4-5% of Crohn’s disease patients. The condition is caused by inflammation in the fatty layer of the skin, and is usually reflective of the underlying intestinal inflammation, flaring up along with an IBD flare. 

Erythema Nodosum manifests as bumps beneath the skin surface, 1-5 cm in diameter. They usually appear on the hands and feet and can resemble bruises although they are not always visible. The bumps can feel like painful, tender nodules. EM flares are often accompanied by fever, chills, and joint pain. 

Treatment of EN generally involves treating the underlying IBD, as the skin condition generally subsides on its own with IBD management. 

Pyoderma Gangrenosum 

Pyoderma Gangrenosum (PG) is another skin condition driven by immune dysregulation affecting 1-3% of IBD patients. 

Although linked to the underlying inflammatory condition, skin flares do not seem to correlate with intestinal flares. In cases of pyoderma gangrenosum, the condition begins as skin nodules but then spreads and forms ulcers filled with pus. 

The condition is more severe than Erythema Nodosum and requires dermatological therapy with either topical medications such as antibiotics, steroids, 5-ASA, or systemic steroid therapy. Some cases may require oxygen treatment, biologic therapy, or a range of other medications. 

Anal Fissures 

Anal fissures are small tears in the skin around the anus that cause pain during bowel movements. Although quite rare in cases of UC, fissures are unfortunately more common in those with Crohn’s disease. 

Fortunately, fissures generally heal on their own. In the meantime, warm baths, ointments containing nifedipine and/or nitroglycerin which relax the anal muscle to allow healing, and natural ointments such as aloe vera may ease the pain, reduce swelling, and help the skin heal. 

Eye Conditions in IBD 

Some 10% of IBD patients also experience some kind of eye condition. Although eye conditions in IBD are usually not serious and usually resolve with successful management of the underlying condition, it’s best to alert your doctor if you notice any type of eye irritation or inflammation so it can be treated effectively. 

Uveitis 

One of the most common is uveitis, which is the painful inflammation of the uvea – the middle layer of the eye wall. 

Symptoms of uveitis include: 

  • Pain
  • Blurred vision
  • Sensitivity to light
  • Redness of the eye 

Like many extra-intestinal manifestations of IBD, uveitis usually resolves once the intestinal inflammation is under control. However, you should consult an ophthalmologist who may prescribe special eye drops containing steroids to manage the inflammation. If left entirely untreated, uveitis may develop into glaucoma and potential loss of vision. 

Episcleritis 

The most common eye complication associated with IBD is episcleritis, a type of red eye caused by inflammation in the episcleral tissues (the tissues between the whites of the eye and the lining of the inner eyelid). 

The condition is considered an indicator of active IBD, and treatment usually involves targeting the underlying IBD inflammation. 

Keratopathy 

Some patients with Crohn’s disease may develop keratopathy, which is an abnormality of the cornea.

Symptoms of keratopathy include:  

  • Red eyes 
  • Feeling like you have something in your eye (foreign body sensation) 
  • Eye pain
  • Sensitivity to light
  • Watery eyes
  • Blurred or decreased vision

Dry Eyes

Dry eyes, or keratoconjunctivitis sicca (KCS), can develop in IBD patients due to a vitamin A deficiency. The condition is caused by a decrease in tear production, and can in some cases lead to an eye infection. Artificial tears may provide relief of symptoms, and vitamin A supplements can be taken to compensate for the deficiency.

Kidneys Complications in IBD 

Serious kidney complications associated with IBD are rare, but some less serious ones occur more frequently.

Kidney Stones 

Kidney stones are probably the most common kidney disorder associated with IBD, especially Crohn’s disease. This is because Crohn’s disease of the small intestine hinders fat absorption, which can lead to a case of oxalate kidney stones.  

Symptoms of kidney stones: 

  • Sharp pain
  • Nausea 
  • Vomiting
  • Blood in the urine. 

Treatment for kidney stones generally requires more fluid intake as well as a low-oxalate diet rich in vegetables and juices. If the stones do not pass independently, they may have to be surgically removed. 

Hydronephrosis 

Hydronephrosis is a condition in which an obstruction disrupts the natural flow within the tubes connecting the kidneys to the bladder, called ureters. Hydronephrosis predominantly impacts the right kidney, positioned in close proximity to the terminal ileum—a segment of the small intestine commonly affected by Crohn’s disease. 

The pressure exerted by a diseased terminal ileum upon the connected ureter blocks urine drainage into the bladder. This blockage then triggers the abnormal enlargement of the kidney and the formation of scar tissue. 

Patients may experience persistent, dull pain in the kidney area, and the presence of blood or pus in urine, which should not be ignored as surgical intervention may be necessary to restore urinary flow. 

Amyloidosis 

Amyloidosis arises from an abnormal amount of a protein called amyloid in various organ tissues. This can impact the kidneys, especially in Crohn’s disease, although this condition is rare and is the outcome of long-term and severe continuous inflammatory activity. 

Liver Complications in IBD 

IBD can lead to liver inflammation and damage in some patients. While most liver damage is reversible, approximately 5% of individuals with IBD may experience severe liver disease. 

Primary Sclerosing Cholangitis (PSC) 

PSC is an immune-driven inflammation of the bile ducts, the small pipes that convey the bile generated in the liver to the gallbladder and from there to the small intestine to help with the digestion of food. 

PSC occurs in the general population but affects patients with IBD more commonly, especially those with IBD affecting the colon. The disease can present with damage to the bile ducts, causing accumulation of bile manifesting as jaundice. 

Recurrent itchiness (pruritus) is an early sign sometimes. This liver disease can be diagnosed by special imaging techniques such as MRI MRCP and requires follow-up and treatment with liver specialists.

Hepatitis 

Hepatitis involves the inflammation of the liver, often caused either by autoimmune hepatitis or by certain medications used for IBD. 

Medications that may disrupt normal liver function include methotrexate, azathioprine, 6-mercaptopurine (6MP), and, rarely, anti-tumor necrosis factor (anti-TNF) agents, which can induce hepatic injury. Your healthcare providers should closely monitor your liver health when using these medications so they can promptly address any concerning symptoms.

Those with IBD may also experience liver inflammation caused by autoimmune hepatitis, a condition in which the immune system mistakenly attacks liver cells. Viral infections, such as hepatitis A, B, or C, can also contribute to liver inflammation in IBD. 

Anemia 

Patients with ulcerative colitis (UC) are particularly vulnerable to iron deficiency anemia due to the associated blood loss, while patients with Crohn’s disease mostly suffer from problems in iron absorption leading to anemia.

Signs indicating iron deficiency anemia may include:

  • Fatigue and weakness
  • Pale skin
  • Cold hands and feet
  • Brittle nails
  • Rapid heartbeat or shortness of breath
  • Headaches, dizziness, or lightheadedness
  • Unusual cravings for substances like ice, clay, soil, or paper

Managing iron-deficiency anemia solely through dietary adjustments and supplements can be challenging and may require intravenous (IV) iron therapy.

If you experience any of the aforementioned symptoms, it is strongly advised to promptly inform your physician to discuss appropriate management strategies.

author

Evinature

DISCLAIMER

This blog is not intended to provide diagnosis, treatment, or medical advice. The content provided is for informational purposes only. Please consult with a physician or healthcare professional regarding any medical or health related diagnosis or treatment options. The claims made regarding specific products in this blog are not approved to diagnose, treat, cure, or prevent disease.

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