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"Medical Journeys" is a set of clinical resources reviewed by physicians, meant for the medical team as well as the patients they serve. Each episode of this 12-part journey through a disease state contains both a physician guide and a downloadable/printable patient resource. "Medical Journeys" chart a path each step of the way for physicians and patients and provide continual resources and support, as the caregiver team navigates the course of a disease.

Ulcerative colitis (UC) is a relatively common though still not fully understood autoimmune condition affecting the large intestine. In this initial installment of the "Medical Journeys in Ulcerative Colitis" series, we review who is affected, what exactly goes wrong, and the typical disease course.

Epidemiology of Ulcerative Colitis

In developed countries including the United States, UC affects roughly 300 people per 100,000 population, with an annual incidence in the neighborhood of 10 per 100,000. Unlike most autoimmune diseases, UC does not seem to discriminate by sex, as incidence and prevalence rates are nearly the same in men and women.

The most common age for UC to appear is early adulthood. However, it can strike at almost any age. One recent found that, in 2018, just over 35% of new cases were in people ages 17-40, with about 25% of new cases in both adolescents and in those age 40 and older. (The same data also indicated that these rates have changed considerably since 2000, with older individuals showing incidence falling by roughly one-third while it doubled in the 10-16 age group.)

Globally, the highest prevalence of UC has been observed in wealthier nations. Multiple hypotheses for this observation exist, including diet and other environmental triggers. Some support for that now comes from developing countries such as Brazil, China, and South Korea, where as Western-style foods have become increasingly available.

With respect to race/ethnicity, data suggest that people of European ancestry are at the highest risk for UC (although that might be a function of dietary patterns, at least in part). Population-level data in the U.S. are hard to come by -- most studies have focused on the broader category of inflammatory bowel disease (IBD), lumping UC together with its cousin, Crohn's disease -- but a showed prevalences of 0.69% for white Americans, versus 0.37%-0.43% for all other major ethnicities.

Pathophysiology of Ulcerative Colitis

As the name suggests, UC is indeed an inflammatory disorder in the colon. Inflammation is most typically found in the rectum but it can extend proximally to the cecum.

The main issue is that the epithelial layer lining the colon is compromised and becomes more porous. This allows other cell types in the deeper tissues to become involved as well, with their dysfunction contributing to the histologic pathology and clinical symptoms.

As epithelial porosity increases, underlying tissues, including their immune components, are exposed to substances such as luminal microbial components from which they would normally be shielded. These components may be from nonpathogenic bacteria that make up the healthy gut microbiome; but now coming into contact with deeper tissues, an inflammatory reaction results.

As , these microbial antigens appear to activate the innate immune system via interactions with macrophages and dendritic cells. The adaptive immune system gears up, too, as examination of patient tissue samples has shown disruption in the balance between regulatory and effector T cells and increased natural killer cell activity. Cytokines are released -- most notably tumor necrosis factor (TNF) alpha.

Ultimately the result is ulceration of the interior colon and the clinical symptoms of abdominal cramping, fecal urgency, and diarrhea. The colon may shorten and haustral markings (which give the colon its segmented appearance) fade; however, the colonic lumen remains relatively intact.

While these symptoms overlap to some degree with those of Crohn's disease, the . In Crohn's disease, the lumen shrinks markedly and the exterior develops a fatty sheath, while the interior develops a bumpy "cobblestone" texture. As well, UC generally affects one continuous segment of the colon with a clear border, whereas Crohn's is typically patchier with inflammation sometimes affecting the small intestine, too.

What triggers UC development in the first place will be the subject of the third installment in this series. Suffice it to say here that it appears to be a combination of genetic factors and environmental influences. Diet is obviously among the latter but it is not the only one.

Natural History of Ulcerative Colitis

There is no single disease course that applies to all patients. Indeed, identified four broad patterns:

• An initial burst of disease activity followed by long-term partial or complete remission

• Chronic but intermittent symptoms

• Chronic and continuous disease

• Increased activity after a period of mild symptoms

That review found the first pattern to be easily the most common, experienced by more than half of patients; the second accounted for about one-third.

Of course, treatment in most cases can relieve if not eliminate symptoms. Therapy will be addressed in a later installment in this series. It's important to note, however, that current therapies are not curative, in the sense of permanent remission following a set course of treatment; most patients who respond to treatments must continue with them indefinitely. Also, some patients who do respond will still face disease progression.

First-line medical therapy with drugs such as mesalamine or 5-aminosalicylates will lead to symptom improvement in most patients. Clinical trial data (as summarized in mesalamine's label) indicate that about one-quarter will obtain remission. Patients with inadequate responses or showing progression while on first-line treatment may eventually proceed to biologic drugs such as adalimumab (Humira, Amjevita).

Even when managed successfully, UC predisposes patients to development of colorectal cancer. The 2017 natural-history review indicated that the risk is more than doubled (standardized incidence ratio 2.4 in pooled data) compared with the general population. Recent studies, however, suggest that , relative to patients managed otherwise. Also, there is no hard evidence to suggest that cancers outside the intestinal tract are more common with UC.

Up next: Making the diagnosis