Introduction

Inflammatory bowel disease (IBD) refers to a general term for conditions causing chronic inflammation of the gastrointestinal tract. Microscopic colitis (MC) is a disease falling under IBDs, more frequently observed in people assigned female at birth of age 60-65 years old, leading to symptoms such as watery diarrhoea. 

The cause of MC remains elusive but is often associated with coeliac disease (CD).¹ CD is an autoimmune disorder that occurs with gluten intake. Consumption of foodscontaining gluten may trigger a series of reactions of the immune system in genetically predisposed individuals, resulting in symptoms such as chronic diarrhoea or constipation, weight loss, abdominal pain and bloating.²

Scientific studies have demonstrated a correlation between MC and CD, with results showing a higher risk of developing CD in patients with MC, particularly in white Europeans.¹ The risk of MC in patients who have been diagnosed with CD is also heightened, with MC typically being diagnosed at an earlier age. This association is presumed to be caused by a specific yet still unknown genetic correlation between the two conditions. Clearguidelines have been established to helpin understanding when these occur side by side, especially since they are displaysimilar symptoms. The accurate diagnosis of these conditions is a crucial factor impacting their management and treatment.³

Causes and effects on the body

Microscopic colitis

MC can be classified into two distinct types each with diverse characteristics; lymphocytic colitis and collagenous colitis. The causes of this condition are not yet completely understood. However, a genetic susceptibility,, may play a role in MC appearance. Additionally, the use of specific medications such as nonsteroidal anti-inflammatory drugs, aspirin, proton pump inhibitors, selective serotonin reuptake inhibitors as well as beta-blockers, angiotensin-converting enzyme inhibitors, and statins have been suggested for possibly provoking MC.⁴

The pathogenesis of MC is thoughtto be caused by defects in the gastrointestinal epithelium, the protective barrier present in the large intestines, and the presence of substances, which can trigger various immune responses and cause inflammation. Furthermore, bile acid malabsorption and increased levels of bile acids in the colon are also believed to potentially induce MC in certain individuals. Moreover, modifications of the bacterial flora of the intestines are believed to play a role in the development of MC, also affecting the composition of bile acids.⁴

Coeliac disease

Coeliac disease is caused by an abnormal immune response to gluten, leading to deficits in the enterocytes of the small intestine. The cause of CD likely lies in hereditary patterns and the presence of specific genes, as observed in most patients. Environmental factors, such as gastrointestinal infections at a young age may also be associated with CD development later in life.⁵ 

The pathogenesis of CD begins when a specific peptide from gluten, gliadin, causes local inflammation in the small intestine, and the destruction of intestinal villi, the fine hair-like structures that line the inside of the small intestine. This destruction of the intestinal surface causes irregularities in the normal function and absorption of the digestive system, further impacting other body systems.⁵

Shared mechanisms

Several epidemiologic studies have identified a correlation between MC and CD, particularly with CD being a significant risk factor for MC. However, their shared underlying mechanisms still need to be clarified. Nevertheless, similarities in the presence of specific genes seem to be responsible for the development of both diseases. Moreover, scientists suggest similarimmunological pathways in MC and CD development, as both are related to increased levels of distinct inflammatory cytokines. Understanding the exact mechanisms and causesof the two conditions and identifying if they are relatedare crucial to deciding an appropriate treatment plan.⁶

Overlapping symptoms of microscopic colitis and coeliac disease

Symptoms between MC and CD can have numerous similarities. Their evolution even during the first-line treatment (e.g., excluding gluten from diet) must be considered for differential diagnoses or concurrency.⁷

Generally, symptoms of MC can include:⁷

• Chronic watery diarrhoea without blood, which can lead to dehydration
• Abdominal pain
• Weight loss or malnutrition
• Foecal urgency

CD symptoms are similar to MC and further include intolerance to gluten, bloating, and fatty stool. The chronic inflammatory state in patients with CD also negatively affects the absorption of essential nutrients and secretion of water and solutes, as well as the digestion of food.⁷

Codiagnosis of microscopic colitis and coeliac disease

Symptoms of MC and CD can be confusing as many causative agents may be associated with diarrhoea. Following specific diagnostic methods is essential for ruling out different pathologies, such as chronic diarrhoea. Specifically, the diagnosis of MC initially involves a stool culture to identify the presence or not of pathogens, which can cause diarrhoea.

Colonoscopy procedures are typically performed to investigate indicative signs of MC, although the endoscopic appearance of patients is not specific enough to make conclusions. Therefore, during the colonoscopy, samples from specific colon segments (usually ileocolonoscopy) are also obtained for biopsy, to examine the histologic characteristics of the tissues, specific for either collagenous or lymphocytic colitis.¹ 

Furthermore, patients with MC are often recommended to be screened for CD since the relatively high incidence of this condition indicates a possible association. Thus, further testing for CD may be required. Finally, according to treatment response, certain patients may also need to be tested for bile acid diarrhoea.⁸

Patients with malabsorption and diarrhoea, as well as other typical symptoms of CD, are usually suspected and screened for CD. However, certain patients may present with less common symptoms or even be asymptomatic, thereby rendering detection of CD a rather troublesome task. 

Some of the strategies that are recommended for improving detection rates include serologic testing, particularly in patients with suspected CD or those with a hereditary risk. The diagnosis of CD is predominately based on antibody serologic tests and biopsies of the small intestines mucosa. Histological findings can also indicate the presence of CD and could include local inflammation and villous atrophy.⁹

Management of coexisting microscopic colitis and coeliac disease

Since co-diagnosis of MC and CD can be challenging, patients may be initially treated for one of the two conditions. In detail, MC management begins primarily by:^7,8

• Discontinuing any medications that may cause the disease. 
• A specific diet plan, avoiding caffeine and lactose
• For mild symptoms, anti-diarrhoea medications, such as loperamide, seem to be effective and are commonly used
• Other medications, including steroids, bismuth subsalicylate, and bile acid sequestrants can be used, with budesonide being specifically recommended as the first-line of treatment

There are cases, however, where patients with MC do not respond well to the first-line of treatment and thus require further testing to identify other potential causes of diarrhoea. If CD is indicated, then a change in the treatment plan may be needed to relievesymptoms.⁶ Specifically, CD management includes:⁹

• A strict gluten-free diet, avoiding products such as wheat, barley, or rye. Patients should be educated on correctly identifying foods that contain gluten by reading the labels and avoiding any contamination of foods or utensils. Depending on each country, reimbursement may be provided to patients on a gluten-free diet, as this diet can be relatively expensive. Referring to a dietician would also help in adopting a balanced diet
• Intake of a low dose of gluten if it cannot be completely avoided. Less than 10mg is considered safe for most patients with CD and does not cause alteration in the intestinal mucosa. Oats are also safe for most CD patients, though introducing them to the diet should be done cautiously, checking for possible adverse events
• Continuous monitoring because a gluten-free diet may limit the intake of specific nutrients. Testing for iron deficiency anaemia, vitamin B12 and vitamin D deficiencies among others, is highly recommended

As in MC, certain patients diagnosed only with CD, may not show an optimal response despite adhering to the recommended treatment methods and following a gluten-free diet, thereby requiring testing for another disease that causes diarrhoea. MC may be a concomitant condition and should be managed accordingly.⁶

Summary

In summary, MC refers to a type of IBD, which causes chronic inflammation in the colon. The causes of MC are not completely understood but factors such as genetics, hereditary patterns and specific medications may be related to MC development. A disruption of the intestinal epithelial barrier due to immune responses, bile acid malabsorption, and irregularities in the intestinal bacterial flora are some of the characteristic yet not specific pathophysiological findings in patients with MC. The presence of an autoimmune disease, including CD, is also a potential risk factor for MC. 

Patients with this disease often exhibit symptoms such as watery diarrhoea, abdominal pain, and weight loss, and must seek medical aid to properly diagnose this condition. European guidelines for MC management primarily suggest the use of anti-diarrhoea medications for mild disease and budesonide for more severe symptoms.

CD is an autoimmune condition that affects people who cannot digest gluten. In patients with CD, gluten causes a series of immune reactions that lead to inflammation of the small intestines, and possibly a destruction of intestinal villi. The causes of CD primarily rely on the presence of specific genes and hereditary patterns, with certain infections in childhood also considered risk factors for CD in adulthood. 

The main symptom of this disease is watery diarrhoea, along with bloating, abdominal pain and fatty stool. Adhering to a gluten-free diet and following dieticians’ recommendations on a balanced diet, along with routine testing for certain nutrient deficiencies are usually effective strategies for managing CD.

MC and CD have been provenly correlated, according to numerous epidemiologic studies and can occur simultaneously. Patients with a suspected MC should be tested for CD, as evidence suggests a high incidence of coexistence. Finally, testing for both conditions is pivotal, particularly in patients who do not respond to the first-line of treatment for one of the two diseases and may require further adjustments in their management plans.