Ischemic colitis (IC) is a disorder characterised by inflammation of the colon as a result of reduced blood flow. More recent evidence suggests that autoimmune disease may be a risk factor for IC. In this article we will explore IC in more detail, understanding its risk factors, symptoms, and diagnosis. We will then look into autoimmune diseases and finally explore recent research which suggests a link between IC and autoimmune disease. 

Understanding ischemic colitis

Explanation of ischemic colitis

IC is defined as the inflammation of the colon (large intestine) due to reduced blood flow. The reduced blood flow to the colon results in oxygen and nutrient deprivation. Because of this, an inflammatory response is triggered which is responsible for causing the characteristic inflammation of the colon.¹

Causes

The most common causes of IC include:

• Atherosclerosis 
• Low blood pressure
• Bowel obstruction
• Inflammation of blood vessels

Symptoms 

• Pain and tenderness in the belly
• Blood in stool
• Sudden bowel movements
• Diarrohea 
• Nausea

Diagnosis

IC is easily misdiagnosed due to its high similarity to other diseases, particularly inflammatory bowel diseases (IBD). Several diagnostic tools can be used to help identify IC, these include:

• Abdominal CT scans - these provide images of the colon and are useful for ruling out other disorders
• Colonoscopy - this allows the physician to view the colon, take biopsies if needed, and provide detailed images of the colon, all of which can help aid in the diagnosis
• Stool analysis - This can be used to rule out infection, assess for blood, as well as look for subtances in the stool linked to various conditions affecting the colon

Risk factors

• Surgery
• High cholesterol
• Age
• Gender

Autoimmune diseases

Explanation of autoimmune diseases

Autoimmune diseases are disorders whereby the immune system mistakenly attacks the body’s own cells. The fundamental role of the immune system is to detect anything in the body that is ‘non-self’ - in other words, anything that does not belong to the body. Immune cells in the immune system are specialised to interact with other cells, whether they are self or non-self. Normally, immune cells do not react or trigger an immune response when interacting with a host (self) cell; they are designed to only react to pathogens or mutated cells.²

Mechanism of autoimmune reaction

In the immune system, antibodies bind to pathogens and mark them for removal by the immune system. Antibodies are proteins which are specific to certain pathogens and express components on their surface that can recognise pathogens and non-self cells. Specialised immune cells, known as B-cells, are the source of antibodies. These cells originate from the bone marrow and develop into their mature form there before being released. All cells begin as stem cells (think of those as the origin of all specific cells – in the right environment, stem cells can develop into any cell)and later become specialised and with a set function. Once developed, B-cells are tested for autoreactivity (whether they react to the body’s own cells). Autoreactive B-cells are filtered out, and those that are not autoreactive undergo further processing, whereby they become fully developed B-cells that play a role in the immune system.³

Exploring the Link: ischemic colitis and autoimmune disease

Case studies suggesting a connection

Although rare, cases have been reported whereby some autoimmune diseases have been linked with ischemic colitis. One of the more common cases is the manifestation of IC alongside systemic lupus erythematosus (SLE), more commonly known as Lupus. SLE is an autoimmune disorder which can affect many parts of the body, including the digestive system. 

Case 1

A patient aged 64 with a past medical history of SLE presented with sudden left lower abdominal pain and bloody diarrhoea. Colonoscopy revealed acute inflammation and microscopic changes that were consistent with the characteristics of IC.⁴

Case 2 

A 57-year-old female patient with a history of SLE had been experiencing abdominal pain and vomiting. Her vital signs were normal, with a tenderness in the left lower abdomen documented. Abdominal CT scans showed thickening of the large intestine, a sign of inflammation in the area. A colonoscopy revealed mucosal inflammation with bleeding and ulceration. IC with increased SLE activity was confirmed as the diagnosis.⁵

Case 3 

A 32-year-old male diagnosed with SLE was admitted to the hospital with reported abdominal pain and bloody stool. Tenderness of the left lower abdomen was confirmed after a physical examination. Severe inflammation of the lining of the intenstines was identified during flexible sigmoidoscopy (a camera test exploring the end segments of the colon) and irregular ulceration. Samples of the intestines viewed under a microscope showed a large number of Inflammatory cells and bleeding of the mucosa. Ischemic colitis with increased SLE activity was confirmed as the diagnosis.⁶

Potential mechanisms linking autoimmune diseases to ischemic colitis

Research into the link between autoimmune diseases and IC is in its infancy, therefore, the mechanisms responsible for this relation between both disorders are unknown. However, research has previously established links between ulcerative colitis (UC) (a type of inflammatory bowel disease) and autoimmune diseases, and may suggest a similar, potential relationship between IC and autoimmune disease. 

Ulcerative colitis and autoimmune disease

UC is a condition characterised by inflammation of the colon and rectum. Unlike ischemic colitis, where a lack of blood supply affects the colon, UC begins in the tissues of the colon itself. The symptoms, however, are very similar. The consensus is that UC is an autoimmune disease, with the most popular theory being that the immune system mistakenly attacks the good bacteria present in the lining of the colon, leading to inflammation. The autoimmune mechanism that causes this is currently unclear – many experts believe that it is a combination of genetic and environmental factors. UC is also thought to be a risk factor for ischemic colitis, as autoimmunity in the colon can lead to reduced blood flow.⁷

Crohn’s disease and autoimmune disease

Crohn’s disease (CD) is also an inflammatory bowel disease (IBD), and like UC, it is also widely considered an autoimmune disease. Although the exact mechanism is unclear, the immune system in the lining of the colon is thought to be partly responsible for the inflammation and may be triggered by food and bacteria. Several theories have been proposed, however, they are still in their infancy.⁸

Clinical implications and management

Importance of early diagnosis

Early diagnosis of IC can help prevent the worsening of symptoms and further complications such as immune dysregulation, gut microbiome alterations, and tissue injury that are irreversible and stem from IC. However, IC is a complicated disorder therefore early diagnosis can be made complicated. 

Treatment strategies for ischemic colitis in patients with autoimmune diseases

In patients diagnosed with ischemic colitis that was a result of an autoimmune disease, treatment strategies targeting the immune system should be prioritised. Treatments for autoimmune diseases can include the following:

• Corticosteroids – these dampen immune system overactivity 
• Anti-inflammatory drugs – these can help reduce inflammation 
• Painkillers – these can help relieve pain 
• Antibiotics – these can help fight bacterial infections, which may complicate any existing inflammation in the colon 

In some cases, surgery to help unblock the blood vessels in the affected area, or remove an area of the colon that is no longer functioning, may be required.

Prognosis and long-term management

The prognosis and management of ischemic colitis can vary significantly from individual to individual. Therefore, it is important that a personalised and tailored plan is used for each patient. 

Future directions and research opportunities

Areas for further investigation

More research is needed to establish the link between IC and autoimmune disease. The evidence so far, though in its infancy, provides an interesting new link to which autoimmune disease may well be a cause for IC. More evidence is needed to unravel the underlying mechanisms by which autoimmune disease may lead to the onset of IC. Through understanding this, a more comprehensive understanding of the causes of IC can be elucidated. This may help improve current diagnostic tools, and can in turn enable a more tailored approach to those with a medical history of autoimmune disease and IC. 

Summary

Ischemic colitis (IC) is a disorder characterised by inflammation of the colon due to obstructed blood flow. More commonly, causes such as atherosclerosis, low blood pressure and inflammation of blood vessels have been associated with IC. New research suggests that autoimmune disease may also be a cause. Autoimmune disease occurs when the immune system mistakenly attacks cells of the body (self-cells) causing damage. Systemic Lupus Erythematosus (SLE), which is a type of autoimmune disease, has been reported in some patients diagnosed with IC. This link suggests that autoimmune disease may potentially be a factor in the onset of IC. Although research is in its infancy, this possible link between IC and autoimmune disease provides an interesting new insight into how IC could be managed in the future. With the likes of ulcerative colitis (UC) and Crohn’s disease having been categorised as autoimmune disorders, this may shine a light on the link between autoimmune disease and GI disorders more generally.