Crohn's disease (Crohn disease) - causes, symptoms & pathology

Summary

Crohn disease is a chronic inflammatory condition that can affect any part of the gastrointestinal tract from mouth to anus. Unlike ulcerative colitis, Crohn's inflammation is transmural, patchy, and can produce granulomas, ulcers, and a cobblestone appearance. The script describes immune-related causes — genetic risk (including NOD2/CARD15 frameshift mutations), epithelial barrier defects that let pathogens provoke antigen presentation, and an exaggerated Th1 cytokine response (interferon gamma and TNF alpha) that recruits macrophages and destructive mediators. Common symptoms include abdominal pain, diarrhea, bleeding, and malabsorption. Treatment centers on anti-inflammatories, antibiotics, immunosuppressants, and sometimes surgery.

Takeaways

• 😀 Crohn's disease (also called Crohn disease) is an inflammatory bowel disease that can affect any part of the gastrointestinal (GI) tract, from mouth to anus.
• 😀 Unlike ulcerative colitis, which only affects the large intestine, Crohn's disease causes inflammation and tissue damage throughout the GI tract.
• 😀 Crohn’s disease is not classified as an autoimmune disease but as an immune-related disorder. It is thought to be triggered by foreign pathogens in the gastrointestinal tract.
• 😀 The immune system reacts to pathogens like Mycobacterium paratuberculosis and Pseudomonas, but this response becomes dysregulated, leading to excessive inflammation.
• 😀 The immune system's inflammatory response in Crohn's disease leads to damage of healthy tissue in the GI tract, including the release of cytokines, proteases, and free radicals.
• 😀 Genetic factors, including mutations in the NOD2 (CARD15) gene, contribute to the development of Crohn's disease, making individuals with family histories more likely to develop it.
• 😀 The intestinal wall in Crohn's disease may allow pathogens to pass through more easily, triggering an immune response that leads to inflammation and ulceration.
• 😀 Crohn’s disease causes transmural inflammation, meaning it affects the full thickness of the intestinal wall, unlike ulcerative colitis, which only affects the mucosal and submucosal layers.
• 😀 Patients with Crohn's disease often experience symptoms like abdominal pain (especially in the right lower quadrant), diarrhea, and blood in the stool due to tissue damage in the GI tract.
• 😀 Treatment for Crohn's disease involves anti-inflammatory medications, antibiotics, and immunosuppressants. Surgery may be required for severe cases, but removal of affected tissue does not cure the disease.

Q & A

What is Crohn’s disease, and how does it differ from ulcerative colitis?

Crohn's disease is an inflammatory bowel disease that causes inflammation and tissue destruction along the gastrointestinal tract, from the mouth to the anus. Unlike ulcerative colitis, which only affects the large intestine, Crohn's disease can affect any part of the GI tract, with inflammation extending deeper into the intestinal wall (transmural damage), whereas ulcerative colitis only affects the mucosa and submucosa.

What causes Crohn's disease, and how does the immune system play a role?

Crohn’s disease is believed to be triggered by foreign pathogens, such as Mycobacterium paratuberculosis and species of Pseudomonas and Listeria, entering the gastrointestinal tract. The immune system reacts by mounting an inflammatory response, but in Crohn's disease, this response is excessive and unregulated, leading to tissue damage.

How does the immune system malfunction in Crohn’s disease?

In Crohn’s disease, the immune system's response to pathogens becomes unregulated. The immune cells, including T helper cells and macrophages, release excessive cytokines, proteases, free radicals, and other inflammatory substances that lead to tissue damage and inflammation. This dysfunctional response is thought to be influenced by genetic factors.

What role does genetics play in Crohn’s disease?

Genetics plays a significant role in Crohn's disease, as individuals with a family history of the condition are more likely to develop it. Specific genetic mutations, such as a frameshift mutation in the NOD2 gene (also known as CARD15), have been identified as contributing to the disease.

What is the NOD2 gene, and how does a mutation affect Crohn’s disease?

The NOD2 gene is involved in immune system signaling. A frameshift mutation in this gene leads to abnormal protein production, which disrupts the immune response, potentially contributing to the chronic inflammation seen in Crohn’s disease.

What are granulomas, and how do they relate to Crohn's disease?

Granulomas are clusters of immune cells that form in response to inflammation. In Crohn's disease, granulomas form in the affected areas of the gastrointestinal tract as the immune system attempts to contain what it perceives as foreign invaders, though these clusters can contribute to further tissue damage.

What distinguishes the inflammation in Crohn’s disease from that in ulcerative colitis?

In Crohn’s disease, inflammation affects all layers of the intestinal wall (transmural), while in ulcerative colitis, the inflammation is confined to the mucosa and submucosa. Additionally, Crohn’s disease presents with patchy areas of inflammation, giving it a 'cobblestone appearance,' while ulcerative colitis shows continuous inflammation.

What are the common symptoms of Crohn's disease?

Common symptoms of Crohn's disease include abdominal pain (often in the right lower quadrant), diarrhea, blood in the stool, and malabsorption of nutrients. Pain is associated with inflammation, particularly in the ileum, and diarrhea results from damaged intestinal tissue and impaired water absorption.

How is Crohn’s disease treated?

Treatment for Crohn's disease typically involves anti-inflammatory medications and antibiotics to control symptoms. Antibiotics help reduce bacterial overgrowth and curb the immune response. In severe cases, corticosteroids or other immunosuppressants may be prescribed. Surgery to remove affected tissue may be considered, but it does not cure the disease, as inflammation can recur anywhere along the GI tract.

Can surgery cure Crohn's disease?

No, surgery cannot cure Crohn's disease. Although affected tissue can be surgically removed, the disease can recur anywhere along the gastrointestinal tract, meaning that removing tissue does not eliminate the underlying condition.