Inflammatory Bowel Disease

TL;DR. Two diseases in which the immune system attacks the gut. Ulcerative colitis affects only the colon, only the innermost lining, and continuously from the rectum upward. Crohn's disease can affect anywhere from mouth to anus, in patches with normal bowel in between, and it burrows through the full thickness of the wall, which is why it produces strictures, abscesses, and fistulas while colitis does not. That single anatomical difference explains almost every clinical difference between them, including why removing the colon cures ulcerative colitis and does not cure Crohn's. Both usually begin in the teens and twenties, both are lifelong, and both are rising sharply in countries that have recently industrialised, which points hard at environment rather than genes.

Key takeaways

• IBD affects several million people, and prevalence exceeds 0.5 percent in parts of Europe and North America while rising steeply in Asia, South America, and Africa.
• The anatomy is the disease. Full-thickness patchy inflammation (Crohn's) produces strictures and fistulas; superficial continuous inflammation (colitis) produces bleeding and, at the extreme, toxic dilatation.
• Smoking does opposite things to the two diseases. It roughly doubles the risk of Crohn's and worsens it, and it is associated with a lower risk of ulcerative colitis. Nobody should smoke for either reason.
• Faecal calprotectin distinguishes IBD from irritable bowel syndrome cheaply and non-invasively, and it has substantially reduced unnecessary colonoscopy.
• Steroids are for flares only. Using them to maintain remission is a treatment failure, and cumulative steroid exposure causes much of the long-term harm.
• Colectomy cures ulcerative colitis. Surgery does not cure Crohn's, which recurs at the join, which is why the surgical philosophy differs completely between them.

What they are

In short: Two patterns of immune-mediated gut inflammation, distinguished by where they occur and how deep they go.

About 10 to 15 percent of colitis cannot be confidently assigned and is called IBD-unclassified, which is a legitimate category rather than an admission of failure.

Microscopic colitis is a separate condition: chronic watery diarrhoea with a normal-looking colon at endoscopy and inflammation visible only on biopsy. It affects older adults, particularly women, is associated with several drugs including NSAIDs and proton pump inhibitors, and responds well to budesonide. It is a common cause of unexplained chronic diarrhoea in the over-60s and is frequently missed because the colon looks normal.

Don't be confused: inflammatory bowel disease and irritable bowel syndrome are entirely different, and sharing initials has caused real harm. IBD is visible inflammation that damages the bowel, raises cancer risk, and needs immunosuppression. IBS is a disorder of gut-brain signalling with no visible damage (Chapter 60). People with IBD are frequently told they have IBS for years, and a simple stool test now separates them.

The history

In short: Colitis described in the nineteenth century, Crohn's in 1932, and an epidemiological pattern that has been repeating around the world ever since.

Ulcerative colitis was distinguished from infectious dysentery by Samuel Wilks in 1859. Crohn's disease was described in 1932 by Burrill Crohn, Leon Ginzburg, and Gordon Oppenheimer at Mount Sinai in New York as "regional ileitis"; the name attached to the first author alphabetically, to his colleagues' lasting irritation.

The epidemiology is the interesting part. Both diseases were rare before the twentieth century, rose steeply in Western Europe and North America through the mid-twentieth century, and have plateaued at high prevalence there. They are now rising rapidly in countries undergoing industrialisation and urbanisation: China, India, Brazil, the Middle East, and parts of Africa.

Migration studies sharpen the point. Children of South Asian migrants to the United Kingdom develop IBD at rates approaching the host population, far above the rates in their parents' countries of origin. Genes did not change; environment did (Chapter 70).

Treatment milestones: sulfasalazine in the 1940s, corticosteroids in the 1950s, thiopurines from the 1960s, infliximab in 1998 as the first biologic, then gut-selective and cytokine-specific agents from 2014.

What actually goes wrong

In short: A genetically susceptible immune system reacting to the normal gut bacteria across a leaky barrier, in an environment that has changed.

The current model has four interacting components, and the disease appears to require all of them.

1. Genetic susceptibility. Over 240 associated loci. The strongest is NOD2, a bacterial sensor inside cells: variants in it substantially raise Crohn's risk, particularly ileal disease. Others affect autophagy (the cell's process for digesting intracellular bacteria) and the IL-23 pathway. Twin concordance is roughly 30 to 35 percent for Crohn's and 15 percent for ulcerative colitis, which places genes as important and far from sufficient.

2. The gut barrier. The single layer of epithelium plus its mucus coat separates you from trillions of bacteria (Chapter 5). Increased permeability is found in patients and in their unaffected relatives, suggesting it precedes disease.

3. The microbiome. Patients show reduced bacterial diversity and depletion of anti-inflammatory species. Whether this is cause or consequence is unresolved, and it is probably both, forming a loop.

4. Immune dysregulation. The immune response to gut bacteria fails to switch off. In Crohn's the IL-23/Th17 axis is prominent; in colitis the picture differs somewhat. TNF-alpha is central in both, which is why anti-TNF drugs work in both.

Environmental factors with reasonable evidence:

What it does to the body

In short: Diarrhoea, bleeding, pain, and weight loss, plus complications determined by the depth of inflammation, plus disease in joints, eyes, skin, and liver.

Symptoms

Ulcerative colitis: bloody diarrhoea with mucus, urgency, tenesmus (a constant painful sensation of needing to empty an already empty rectum), lower abdominal cramping, and, in severe disease, fever and systemic illness.

Crohn's disease: abdominal pain (often right lower quadrant), diarrhoea usually without blood, weight loss, fatigue, fever, mouth ulcers, and perianal pain or discharge. Because it can affect the small bowel, malabsorption produces vitamin B12 deficiency (terminal ileum), iron deficiency, fat-soluble vitamin deficiency, and, in children, growth failure and delayed puberty, which is sometimes the presenting sign.

Complications

Outside the gut

Roughly a quarter to a half of patients develop extraintestinal manifestations, and they group usefully by whether they track bowel activity:

Primary sclerosing cholangitis (PSC) deserves separate attention. It is progressive inflammation and scarring of the bile ducts, occurring in roughly 5 percent of ulcerative colitis patients, and it is important out of proportion to its frequency: it progresses to cirrhosis and liver failure independently of the bowel disease, it does not respond to any medical treatment, it substantially raises the risk of bile duct cancer and colorectal cancer, and it is a leading indication for liver transplantation in young adults.

Is it deadly?

In short: Mortality is close to the general population with modern treatment, and the burden is disability, surgery, and cancer risk.

Life expectancy in IBD is now close to, though slightly below, the general population in high-income settings. Excess deaths come from colorectal cancer, complications of severe disease and surgery, thromboembolism, and, in PSC, liver disease.

The historical picture was worse. Severe acute colitis had a substantial mortality before effective medical rescue therapy and timely surgery; that is now uncommon in well-resourced settings and remains a genuine risk when treatment is delayed.

Surgery rates have fallen with better medical therapy, and remain substantial: a significant minority of colitis patients eventually need colectomy, and roughly half of Crohn's patients need surgery within ten years, with many needing more than one operation.

Is it contagious?

In short: No. It clusters in families through genes and shared early-life environment.

Inflammatory bowel disease is not transmissible. Neither the inflammation nor the microbiome changes spread between people in any meaningful clinical sense.

Family clustering is real: a first-degree relative of someone with Crohn's has roughly a five to tenfold increased risk. This reflects shared genetics and, likely, shared early-life environment.

The infection question comes up repeatedly because Crohn's granulomas resemble those of tuberculosis, and because Mycobacterium avium subspecies paratuberculosis causes a similar disease in cattle. Decades of investigation have not established it as a cause in humans, and antimycobacterial treatment has not produced convincing benefit. The hypothesis remains open and unsupported.

Who gets it

In short: Teens and twenties, in industrialised and industrialising countries, with a second smaller peak in later life.

• Age: peak onset 15 to 30, with a second smaller peak in the 50s and 60s. Onset in childhood is increasing and tends to be more extensive.
• Sex: roughly equal, with a slight male excess in ulcerative colitis and female excess in Crohn's in some populations.
• Geography: highest prevalence in Northern Europe, North America, and Australasia; rising fastest in newly industrialised countries. A north-south gradient exists within countries.
• Ancestry: notably higher in Ashkenazi Jewish populations, by roughly two to fourfold.
• Family history: the strongest individual risk factor.
• Smoking: as above, in opposite directions.

Treatment, and how it works

In short: Induce remission, then maintain it without steroids, escalating through increasingly targeted drugs, and operate for complications rather than as a last resort.

Treatment has two phases with different tools: induction (getting a flare under control) and maintenance (keeping it under control). Corticosteroids belong only in the first.

Two strategic principles have changed outcomes:

Treat to target, using objective measures. The target is no longer symptom relief but endoscopic healing of the mucosa, because patients whose bowel looks healed have fewer flares, fewer hospitalisations, and less surgery. Symptoms and inflammation correlate imperfectly in both directions.

Early effective therapy in Crohn's. The traditional "step-up" approach, escalating only after failure, is being replaced in higher-risk patients by earlier introduction of biologics, on evidence that this reduces complications and surgery.

Surgery

Ulcerative colitis: removing the colon is curative of the bowel disease. It is done for disease refractory to medical treatment, for dysplasia or cancer, and as an emergency for toxic megacolon or severe bleeding. Reconstruction with an ileoanal pouch avoids a permanent stoma in most cases, at the cost of frequent stools and a risk of pouchitis.

Crohn's disease: surgery treats complications (strictures, fistulas, abscesses) rather than the disease. Inflammation recurs at the join in the majority within a few years, so the philosophy is to preserve as much bowel as possible, using stricturoplasty (widening rather than removing) where feasible, and to restart medical therapy after surgery to delay recurrence. Repeated resections risk short bowel syndrome.

Supporting care, which is not optional

• Nutrition. Exclusive enteral nutrition, a liquid formula diet for six to eight weeks, is as effective as corticosteroids for inducing remission in paediatric Crohn's disease and is first-line in children in many countries because it avoids steroids and supports growth. Its mechanism is not fully understood.
• Iron, B12, vitamin D, and calcium replacement.
• Bone density monitoring with repeated steroid exposure.
• Vaccination before immunosuppression, and live vaccines avoided during it. Infants exposed to anti-TNF drugs in utero should not receive live vaccines in the first months of life.
• Cancer surveillance colonoscopy from 8 to 10 years after diagnosis in colonic disease.
• Smoking cessation, which is one of the most effective single interventions in Crohn's.
• Mental health support. Anxiety and depression are common, worsen outcomes, and are treatable.

What treatment costs

In short: Steroids do the most cumulative damage, thiopurines need a genetic test first, and every immunosuppressant trades inflammation for infection.

• Corticosteroids: the familiar list, plus a specific point here: cumulative lifetime steroid exposure correlates with osteoporosis, cataract, diabetes, and infection, and reducing it is an explicit treatment goal rather than a bonus.
• Thiopurines: marrow suppression (hence genotyping and monitoring), hepatitis, pancreatitis, and an increased risk of lymphoma and non-melanoma skin cancer, the latter meaning sun protection advice matters. The absolute risks are small and the discussion is worth having explicitly.
• Anti-TNF: latent tuberculosis reactivation (screen first), hepatitis B reactivation, serious infection, and loss of response over time from anti-drug antibodies, which is why levels are measured and immunomodulators are sometimes combined to prevent it.
• Vedolizumab: notably fewer systemic infections because it acts on the gut specifically.
• JAK inhibitors: shingles, lipid changes, and the cardiovascular and malignancy signals in older patients with risk factors.
• Surgery: stoma (temporary or permanent), adhesions, and, with repeated Crohn's resections, short bowel syndrome.

What the person can do

In short: Stop smoking if you have Crohn's, do not tolerate ongoing steroids, attend surveillance, and know the emergencies.

• Stop smoking if you have Crohn's disease. It is among the most effective things available and affects both disease activity and surgery risk.
• Do not accept repeated or continuous steroids as a maintenance plan. Needing steroids more than once or twice a year means treatment should be escalated.
• Attend surveillance colonoscopy when it is due. Cancer risk is a real and manageable part of long-standing colonic disease.
• Get anaemia and vitamin deficiencies checked and treated, since fatigue is often as much anaemia as inflammation.
• Take vaccination seriously, and arrange it before starting immunosuppression where possible.
• Know the emergency signs: severe abdominal pain with distension and fever, more than six bloody stools a day with systemic upset, inability to pass stool or wind with vomiting, and any perianal pain with fever.
• Report new joint, eye, or skin symptoms, which may be part of the disease and may change treatment choice.
• Ask about pregnancy in advance. Most drugs are compatible, active disease is the main threat to a pregnancy, and stopping treatment on discovering a pregnancy is usually the wrong move.
• Be sceptical of exclusion diets promoted as cures. Nutrition matters enormously and no diet has been shown to replace medical therapy in adults, and unnecessary restriction worsens malnutrition in a group already at risk.

Living with it

In short: A young person's disease centred on the most private bodily function, with urgency and unpredictability dominating daily life.

IBD begins in the teens and twenties and centres on something people do not discuss. The practical consequences are specific: urgency dictates where someone can go and how long they can travel, incontinence is a real and rarely mentioned fear, and fatigue is pervasive.

Work, education, and relationships are all affected, and schemes providing access to staff toilets exist in several countries because the alternative is that people stay home. Body image after surgery, and living with a stoma, are significant and are handled far better with specialist stoma nursing than without.

Depression and anxiety are roughly twice as common as in the general population, are associated with worse disease outcomes, and are treatable. Psychological therapies aimed at the illness itself improve quality of life and, in some studies, disease course.

What's next

In short: Predicting who needs aggressive treatment early, and making mucosal healing achievable in more than half of patients.

• Better prediction. Most current biologics achieve remission in roughly a third to a half of patients, and choosing between them remains largely empirical. Biomarker and biopsy-based prediction is the main research direction.
• Combination biologic therapy, targeting two pathways at once, in early trials.
• Preventing disease in high-risk relatives, following the identification of pre-clinical markers such as antimicrobial antibodies and altered permeability years before onset.
• Microbiome-directed therapy. Faecal transplantation has shown modest effect in ulcerative colitis in trials and is not yet standard care; defined bacterial consortia are being developed.
• Understanding the global rise, which is the most important question and the least likely to be answered by a drug.

Sources and notes

Global epidemiology and rising incidence in newly industrialised countries: Ng et al., The Lancet, 2017, and Kaplan and Windsor, Nature Reviews Gastroenterology & Hepatology, 2021. NOD2: Hugot et al. and Ogura et al., Nature, 2001. Genetic loci count: Jostins et al., Nature, 2012, and successors. Twin concordance: Halfvarson et al. Smoking's opposite effects: Calkins, meta-analysis, 1989, and subsequent confirmation. Appendicectomy and ulcerative colitis: Andersson et al., NEJM, 2001. Ultra-processed food and Crohn's risk: Narula et al., BMJ, 2021. Migration studies: Probert et al., and UK South Asian cohort data. Crohn, Ginzburg, and Oppenheimer, JAMA, 1932. Infliximab: Targan et al., NEJM, 1997. Vedolizumab: GEMINI trials, NEJM, 2013. Treat-to-target and mucosal healing: CALM trial, The Lancet, 2017. Exclusive enteral nutrition in paediatric Crohn's: multiple trials and ESPGHAN/ECCO guidance. TPMT and NUDT15 genotyping: CPIC guidelines. VTE risk in IBD: Grainge et al., The Lancet, 2010. PSC and cancer risk: standard hepatology references.

Open questions. Why smoking protects against ulcerative colitis while harming Crohn's disease is unexplained. Whether the microbiome changes are cause or consequence is unresolved. What is driving the global rise in incidence is the central unanswered question, with diet, antibiotics, sanitation, and urbanisation all candidates and none established.

Next: inflammation of the blood vessels themselves, including one condition where a few hours of delay costs someone their sight. 👉