Living With Crohn’s Disease

We need bugs. Bugs pollinate plants, decompose dead things, provide food for birds, and make many other vital parts of the ecosystem function. Unfortunately, though they are important, I don’t like bugs in my house. This is problematic because I also like keeping the windows open for a breeze, ocean smells, and to air out the house. To regulate the air coming through the house and keep the bugs out, we use window screens. Unfortunately, the sun, wind, and inexorable march of time degrade screens, and sometimes they tear or separate from the screen frame, letting bugs in. When bugs get into  the house I have a big reaction: chasing bugs, smacking them, smacking my legs, scratching at bug bites, and spraying deadly poison all around the house. A similar breakdown of the boundary between outside and inside can occur in the gut too, and when it does, the body has a similarly intense reaction.

Crohn’s disease is a progressive, destructive, immune-mediated disease that causes areas of alternating inflammation and healthy tissue along the gastrointestinal (GI) tract.^[1] Let’s break that down. Crohn’s is progressive; it gets worse over time. It’s destructive, meaning Crohn’s doesn’t just feel bad, it destroys tissue. Immune-mediated diseases are ones where the bulk of the damage is done by the immune system reacting to some stimulus - like spraying pesticides on fruit to keep bugs off. With Crohn’s, food particles and bacteria get past the gut lining and invade the space behind, called the intestinal lamina propria, where immune cells and signals cause damaging inflammation.^[1]

Crohn’s disease can really bug sufferers, causing intestinal symptoms including:^[1]

• Chronic pain and ulcers

• Diarrhea

• Blood in the stool

Symptoms often follow a remission-relapse cycle alternating between high- and low-symptom periods. Over time, the destructive nature of Crohn’s can lead to complications in and out of the gut. In the gut, Crohn’s disease can cause narrowings called strictures, tunnelling passages called fistulae, bowel tissue damage, and cellular changes that may increase the risk of cancer.^[1,2] Inflammation from Crohn’s may lead to systemic inflammation outside of the gut, affecting the bones, skin, joints, eyes, lungs, liver, and blood vessels.^[1,2]

Crohn’s is caused by a combination of genetic factors, immune system dysfunction, and environmental influences.^[1] Genetic factors can affect how the border cells of the gut, called epithelial cells, regulate what moves through the intestinal wall and how tightly the border cells bind together.^[1,3] Crohn’s affects men and women in equal amounts, and is three to four times more common among people of Ashkenazi Jewish descent. African-American and Asian-American populations have the lowest rates.^[3] Genetics can also affect the immune system, making it less effective at regulating what’s in the gut and/or harsher in its response to perceived threats. Environmental risks include smoking, which doubles the risk of developing Crohn’s, and antibiotics.^[1,3,4] Some medications, like NSAIDs and oral contraceptives, may also have a slight risk attached.^[1,4] Environmental factors that show evidence of a protective effect against Crohn’s include being breastfed, physical activity, exposure to farm animals and pets, and statin cholesterol medications.^[1,4] Changes to the gut microbiome also play an important part in the development and disease activity of Crohn’s; some dangerous bacteria can cross the epithelial layer and survive innate immune responses, causing a swarm of inflammation.^[3]

A cartoon showing a compromised intestinal wall and immune response.

Whatever the underlying cause, the barrier of the gut doesn’t function correctly in Crohn’s disease and it progresses in the same way for most people.^[1] The mucosal lining of the gut degrades, allowing bacteria, toxins, antigens, and food particles to wiggle between the epithelial cells lining the gut.^[1,5] Immune cells detect these “invaders” and start releasing inflammatory molecules, activating killer cells and inflammation cells, and start inflaming the tissue.^[1,5]

Living with Crohn’s is like living in a swamp with no screens on the windows; annoying, painful, and dangerous. Luckily, Crohn’s treatments have been improving rapidly in the last decades. The goal of treatment is to rebuild the intestinal lining and heal intestinal wounds.^[1] Clinical research studies, including the CALM clinical trial, found that aggressively monitoring biomarkers of inflammation and treating early in a relapse cycle has a much better prognosis for healing than relying solely on symptoms.^[6] At the onset of a flare-up, corticosteroids like budesonide and prednisone can offer relatively rapid relief, though they are not to be used for long-term maintenance of Crohn’s.^[1] 

Maintenance therapies are used long-term to extend periods of remission and help rebuild the mucosal lining.^[1] For a long time, classic immunosuppressants have been the go-to for maintenance therapy. Thiopurines limit cell division in fast-reproducing cells (like inflammatory cells) and can help suppress the overreaction of the immune system.^[3] These have been a mainstay, but are now considered inferior in all but low-risk patients - though they are cheaper and typically covered by insurance.^[3,1] Since Insurance companies have decided they know better than doctors, these remain the only medications for many patients. Methotrexate is another common, classic immunosuppressant, though long-term use may increase the risks of serious side effects.^[3]

Biologic medications are a new class of medicines that can treat Crohn’s disease. Molecularly, these are much larger than typical medicines and can target specific parts of the immune system with a much more favorable side-effect profile.^[1] Anti-TNF (anti-tumor necrosis factor) biologics are favored over thiopurines and methotrexate, especially for high-risk patients.^[1] TNF is an inflammatory molecule, so these medications, which include infliximab, adalimumab, and certolizumab, lower inflammation.^[1] Other biologics include the gut-selective anti-integrin (another inflammation molecule) vedolizumab and the inflammation signaling suppressor ustekinumab.^[1] These medications are promising and effective but also very costly. They can offer sustained relief with a more favorable side effect profile than classical treatments. For many, it’s like a new set of screens, letting you enjoy the breeze of daily life without the bite of Crohn’s.

Creative Director Benton Lowey-Ball, BS, BFA

References:

[1] Roda, G., Chien Ng, S., Kotze, P. G., Argollo, M., Panaccione, R., Spinelli, A., ... & Danese, S. (2020). Crohn’s disease. Nature reviews Disease primers, 6(1), 22. https://doi.org/10.1038/s41572-020-0156-2

[2] Peyrin-Biroulet, L., Loftus, E. V., Colombel, J. F., & Sandborn, W. J. (2011). Long-term complications, extraintestinal manifestations, and mortality in adult Crohn's disease in population-based cohorts. Inflammatory bowel diseases, 17(1), 471-478. https://academic.oup.com/ibdjournal/article-abstract/17/1/471/4631202

[3] Torres, J., Mehandru, S., Colombel, J. F., & Peyrin-Biroulet, L. (2017). Crohn's disease. The Lancet, 389(10080), 1741-1755. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(16)31711-1/abstract

[4] Piovani, D., Danese, S., Peyrin-Biroulet, L., Nikolopoulos, G. K., Lytras, T., & Bonovas, S. (2019). Environmental risk factors for inflammatory bowel diseases: an umbrella review of meta-analyses. Gastroenterology, 157(3), 647-659. https://www.gastrojournal.org/article/S0016-5085(19)36709-5/fulltext

[5] Marks, D. J., Rahman, F. Z., Sewell, G. W., & Segal, A. W. (2010). Crohn’s disease: an immune deficiency state. Clinical reviews in allergy & immunology, 38(1), 20-31. https://link.springer.com/article/10.1007/s12016-009-8133-2

[6] Colombel, J. F., Panaccione, R., Bossuyt, P., Lukas, M., Baert, F., Vaňásek, T., ... & D'Haens, G. (2017). Effect of tight control management on Crohn's disease (CALM): a multicentre, randomised, controlled phase 3 trial. The Lancet, 390(10114), 2779-2789. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(17)32641-7/abstract