Crohn's disease

• 1. Introduction

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  Crohn's disease is an inflammatory bowel disease that can strike any segment of the digestive tract, from the mouth all the way to the anus. One in five people living with it is admitted to hospital each year. Within ten years of the first signs, half will need an operation at some point. The illness comes in cycles of flare-ups and remission, and it usually begins in adolescence or young adulthood. This documentary follows the questions it raises. Who first described the disease, and why does its name remain contested? How can one illness show up in the gut, the eyes, the skin, the joints and the mind? Why do some families carry it and some countries see it rise? And how do doctors catch a disease that even a full battery of tests cannot always confirm?

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• 2. A Disputed Name

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  In 1932, a New York gastroenterologist named Burrill Bernard Crohn submitted fourteen cases to the American Medical Association under the heading "Terminal ileitis: A new clinical entity". He worked at Mount Sinai Hospital, alongside colleagues Leon Ginzburg and Gordon Oppenheimer. Later that year the three men published a case series titled "Regional ileitis: a pathologic and clinical entity". Yet the disease did not end up carrying all three names. Crohn's surname comes first in the alphabet, so it became known in the worldwide literature as Crohn's disease.

  Leon Ginzburg, who lived from 1898 to 1988, later provided strong evidence that he and Oppenheimer, who lived from 1900 to 1974, were the first to study the illness. Crohn's own memoir tells it differently, describing his original investigation. The decision to name the disease after him remains controversial.

  A Polish surgeon, Antoni Leśniowski, had described ileitis terminalis as early as 1904. Doctors then could not conclusively separate it from intestinal tuberculosis. In Poland the illness is still called choroba Leśniowskiego-Crohna, which puts his name first.

  Even Leśniowski was not the first to describe inflammatory bowel disease in general. Giovanni Battista Morgagni, who lived from 1682 to 1771, wrote about such conditions. So did the Scottish physician Thomas Kennedy Dalziel, in 1913. The 1932 papers focused on inflammation of the terminal ileum, the part of the small intestine the disease most commonly affects, and that spot shapes much of what patients feel.

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• 3. Inside the Gut

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  Many people with Crohn's disease live with symptoms for years before anyone puts a name to them. The usual onset is in the teens and twenties, though it can occur at any age. Abdominal pain is a common first symptom, especially in the lower right abdomen. Flatulence, bloating and abdominal distension often add to the discomfort.

  Diarrhea is usually non-bloody, though in some cases it contains blood. Where the inflammation sits changes the pattern. Ileitis typically produces large-volume, watery feces, while colitis tends to produce smaller amounts at greater frequency. In severe cases a person may have more than 20 bowel movements a day and wake at night to go.

  Visible blood is less common than in ulcerative colitis, but it is not unusual. It may be bright red, dark maroon or even black, depending on where the bleeding starts. In severe Crohn's colitis the bleeding may be copious.

  Around the anus, itching or pain can point to fissures, fistulae or abscesses. Perianal skin tags are also common. In the mouth, recurrent canker sores are frequent, though it is unclear whether Crohn's disease or the general population's habit of getting them explains that. Some people develop a cobblestone appearance inside the mouth.

  The stomach is rarely the main site. Isolated stomach involvement accounts for less than 0.07% of gastrointestinal Crohn's disease. Recent studies suggest the upper digestive tract is involved in 13-16% of cases, and those symptoms typically appear after the lower ones.

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• 4. Beyond the Bowel

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  As many as 30% of children with Crohn's disease may suffer stunted growth, and for many of them it is the first clue. The disease can arrive just as puberty brings a growth spurt. In older people the sign is more often weight loss, because eating tends to hurt and appetite fades. Extensive small intestine disease can add malabsorption of carbohydrates and lipids.

  The eyes are a common target. Uveitis, inflammation inside the eye, brings blurred vision, pain and sensitivity to light, and it can cost a person their sight if untreated. Researchers think signaling proteins named IL-6, IL-10 and IL-17 travel from the bowel through the blood to the eyes.

  Erythema nodosum is the most common skin problem, affecting around 8% of people. It produces raised, tender red nodules, usually on the shins. Pyoderma gangrenosum is rarer, occurring in under 2%, and appears as a painful ulcerating nodule.

  The joints suffer too. The knee is the most common site of the large-joint form of arthritis, and the spine can be involved. Crohn's disease also raises the risk of osteoporosis, and ileal disease raises the risk of gallstones through a shift in how bile acids are reabsorbed. Thrombosis has been reported in 3.1% of people with Crohn's disease.

  The nervous system and mood are not spared. Neurological complications are reported in up to 15% of cases, with seizures, stroke, neuropathy, headache and depression among the most common. Studies find that up to 65% of women with inflammatory bowel disease may have a depression or anxiety disorder.

  At the rarest end, only 12 cases of Crohn's disease involving the larynx have been reported. Nine of those people struggled to breathe.

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• 5. Genes and Geography

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  Brothers and sisters of someone with Crohn's disease are 30 times more likely to develop it than the general population. About half of the overall risk is genetic, and more than 70 genes are involved. The first mutation found was a frameshift in the NOD2 gene, also called CARD15. Other well documented genes include ATG16L1, IL23R, IRGM and SLC11A1. Twin studies add weight: if one twin has the disease, the other has a 55% chance of it too.

  One gene, LRRK2, is also linked to Parkinson's disease. One variant may raise the risk of Crohn's by 70%, while another lowers it by 25%.

  Genes are only half the picture. Tobacco smokers are three times as likely to develop the disease as non-smokers, and smoking raises the risk of flares. Many cases begin after an episode of gastroenteritis. A large retrospective study found that people prescribed doxycycline for acne had a 2.25-fold greater risk.

  Diet seems to matter as well. Crohn's is associated with more animal protein, more milk protein and a higher ratio of omega-6 to omega-3 fatty acids. People who eat vegetable proteins appear to have lower incidence, while fish protein shows no association. Stress is often blamed, yet there is no concrete evidence that it makes the disease worse.

  History offers another clue. The introduction of hormonal contraception in the United States in the 1960s coincided with a dramatic rise in incidence. The disease affects about 3.2 per 1,000 people in Europe and North America and is less common in Asia and Africa. It is more common in northern countries and among Ashkenazi Jews. In Brazil, incidence has climbed 11% a year since 1990.

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• 6. Microbes and Immunity

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  In 2007, the ATG16L1 gene was implicated in Crohn's disease. It is tied to autophagy, a cellular cleanup process, and a fault in it may hinder the body's ability to attack invasive bacteria. A year later, a new theory challenged the older view that Crohn's is a primary T cell autoimmune disorder. It proposed that macrophages release too few signaling proteins, leaving innate immunity impaired and allowing a lasting inflammatory response in the colon, where the bacterial load is high.

  A rival idea blames an overactive Th1 and Th17 response. Current evidence favors a blended model. In it, a weak first-line immune response lets gut bacteria keep stimulating the adaptive immune system, which then damages tissue without restoring tolerance. That is why Crohn's is not classed as a classic autoimmune disease.

  Specific microbes have been suspected. Mycobacterium avium subspecies paratuberculosis, called MAP, causes Johne's disease in cattle, and several studies suggest it plays a causal role in people. The genetic risk for Crohn's overlaps with susceptibility to leprosy, another mycobacterial disease. Adherent-invasive Escherichia coli has also been linked, and Candida colonization shows a tentative association.

  The cold-chain hypothesis points at bacteria such as Yersinia and Listeria, which grow in the cold. A statistical correlation was found between the arrival of refrigeration in the United States and parts of Europe and the rise of the disease. None of these links has been settled.

  Another study suggested that the human immune system evolved alongside parasites, and that modern hygiene has weakened it. When test subjects were reintroduced to harmless parasites, they responded positively.

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• 7. Finding the Disease

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  A colonoscopy is the best single test for Crohn's disease, yet it is only about 70% effective at diagnosing it. The scope lets a gastroenterologist see the colon and the terminal ileum directly and take biopsies. Because 30% of cases involve only the ileum, the doctor must reach the terminal ileum to make the diagnosis. A patchy pattern that involves the colon or ileum but spares the rectum is suggestive.

  Under the microscope, inflammation may span the entire depth of the intestinal wall. Granulomas, clusters of immune cells, are the hallmark finding, yet they turn up in only 21-60% of people. Unlike the granulomas of tuberculosis, they show no cheese-like caseation.

  The small intestine hides from a standard colonoscope. Capsule endoscopy helps, and a 2025 clinical guideline called it a useful adjunct for small bowel disease. A barium follow-through X-ray can show inflammation and narrowing. CT and MRI reveal abscesses, obstructions and fistulae, and MRI is more sensitive than CT for ulceration and inflammation.

  For children, doctors favor magnetic resonance enterography over CT because it uses no ionizing radiation. Ultrasound offers another radiation-free option. Blood tests look for anemia and measure inflammation through erythrocyte sedimentation rate and C-reactive protein. Antibody tests for ASCA and ANCA help to tell Crohn's disease apart from ulcerative colitis.

  Look-alikes abound, including intestinal tuberculosis, Behçet's disease, irritable bowel syndrome and celiac disease. Doctors also classify the disease by behavior: stricturing, penetrating or inflammatory. Where even ulcerative colitis cannot be separated from Crohn's, the label is indeterminate colitis.

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• 8. Treatment and Outlook

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  A short course of a corticosteroid, paired with methotrexate or a thiopurine, is the usual opening move for someone newly diagnosed. Prolonged steroid use has significant side effects, so doctors move toward immunomodulators and biologic drugs such as infliximab, adalimumab and ustekinumab. The monoclonal antibody briakinumab proved ineffective and is no longer manufactured. These drugs suppress the immune system, which raises the risk of infections, yet vaccination rates in people with inflammatory bowel disease are suboptimal.

  Diet is a daily negotiation. Lactose-free eating is the most common restriction, followed by 17.4% of patients against 11.6% of controls. Fibre avoidance is far higher at 52%, compared with 5% of controls. Stopping smoking is strongly recommended, and a food diary can help identify triggers.

  Surgery cannot cure Crohn's disease. After a first resection, the disease usually returns at the join where the healthy ends were rejoined. Another resection may be needed within five years. Doctors grade recurrence with the Rutgeerts score, from i0 for remission to i3 and i4 for moderate to severe. Removing half or more of the small intestine can cause short bowel syndrome.

  Mind and body are linked here. A meta-analysis found that talking therapy, antidepressants and exercise all reduced inflammatory markers in inflammatory bowel disease, with psychological therapies working best. A 2006 survey in Germany found about half of people with the condition used alternative medicine, most often homeopathy, which has no benefit.

  Up to 80% of people are hospitalized at some point, most often in the first year after diagnosis. Most live a normal lifespan, though inflammatory bowel disease caused 47,400 deaths in 2015. Because the risk of bowel cancer is higher, colonoscopy is recommended every 1-3 years, starting eight years after the disease began.

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