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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.

Regrettably, even ulcerative colitis (UC) patients who maintain good symptom control are not cured and do not fully escape certain risks as the years go by. Clinicians and patients should be on the lookout for potential complications, as early detection and treatment nearly always improve the chances of good outcomes. Preventive measures, too, can ameliorate the risks.

Colorectal Cancer

Foremost among the longer-term complications is colorectal cancer. Patients with UC face approximately double the risk of this malignancy relative to the general population, according to ; its authors also observed that colorectal cancer accounts for about 15% of all-cause mortality in people with UC and other forms of inflammatory bowel disease (IBD).

from the American Gastroenterological Association (AGA) call for an initial colonoscopy screening 8-10 years after onset of symptoms (i.e., irrespective of the patient's age), with two purposes: "to reestablish disease extent and also look for evidence of dysplasia." The recommended schedule for subsequent screenings varies according to the extent and location of UC lesions. An exception to this recommendation are patients with primary sclerosing cholangitis, who should start annual colonoscopy at the time of diagnosis due to a particularly increased risk of colorectal dysplasia.

Patients with more than isolated proctitis should be screened every 1-5 years based on individualized risk factors, including disease extent, presence of inflammation, pseudopolyposis, family history of colorectal cancer, and personal history of colonic dysplasia, depending on risk factors.

The AGA guidance also includes specific advice on what to do with non-negative colonoscopy findings. Prior guidelines recommended early referral for surgery for presence of colorectal dysplasia. However, with more recent improvements in high definition white light and dye spray chromoendoscopy and endoscopic resection techniques, there is an increasing role for endoscopic management of colonic dysplasia in UC.

In general, if a lesion is well circumscribed and endoscopically resectable, then endoscopic resection is a reasonable approach. However, recurrent "invisible" and multifocal dysplasia are still indications for referral for colectomy.

Cardiovascular Disease

Numerous studies have documented an increase in cardiovascular risks associated with IBD, as noted in a recent . These run the gamut: atherosclerosis (both coronary and peripheral), venous and arterial thrombosis, arrhythmias, and heart failure.

Guidelines on UC management suggest that patients be screened regularly for signs of cardiovascular disease and reminded about modifiable risk factors such as cholesterol and smoking, etc.

Primary Sclerosing Cholangitis (PSC)

Chronic inflammation in the bowel can, over time, extend to the bile ducts, which can become narrowed or even totally obstructed. A found that PSC occurs in about 2.5% of UC patients.

"Prevalence was generally higher in men, patients with more extensive, compared with left-side, UC," the authors stated. Unfortunately, PSC is not directly treatable, but its symptoms -- fatigue, diarrhea, pruritus, jaundice -- may be relieved with medications. in the most severe cases. As noted above, one of the most important considerations in patients with UC and PSC is the increased risk of colorectal cancer and the need for annual colonoscopy surveillance starting at diagnosis.

Osteoporosis

Bone embrittlement can occur both as a result of chronic inflammation in the body and as a consequence of long-term corticosteroid treatment. (This is one reason treatment guidelines emphasize keeping steroid use to a minimum.) According to the Crohn's & Colitis Foundation, as many as develop osteopenia, the precursor to osteoporosis.

Guidelines focus on prevention, through such measures as limiting alcohol consumption, smoking cessation, and getting plenty of exercise. Vitamin D and calcium supplementation can be helpful if insufficiencies are found (common in UC, as discussed below). If osteopenia is detected, can be considered.

Vitamin/Mineral Deficiencies

Between the effects of UC and measures taken to control it, such as dietary restrictions, patients may suffer from lack of key vitamins and minerals. "Micronutrient deficiencies occur in more than half of patients with IBD," according to a , which listed iron, vitamin D, vitamin K, folic acid, selenium, zinc, and vitamins B1, B6, and B12 as the most common deficiencies. In addition, patients who cut dairy products from their diet may lack sufficient calcium.

Clinicians should monitor for nutrient deficiencies and counsel patients on supplementation and other preventive measures. The Crohn's & Colitis Foundation maintains a to prevent or counter key deficiencies.

Drug Side Effects

Another major consideration for potential complications involves the controller medications used to treat UC. Some long-term effects are quite rare: mesalamine, for example, is known to cause liver injury, but only at a ; kidney damage , but not often. Patients on mesalamine should have routine labs to check for kidney and liver function.

Essentially all UC medications stronger than mesalamine result in some degree of immunosuppression. Some medications may be more targeted than others, but all UC patients and their providers need to be aware of infection risks if using a biologic or immunosuppressant. Some medications, like Janus-associated kinase (JAK) inhibitors may have an extra predilection toward shingles, although all patients who are on or considering immunosuppression should be vaccinated against herpes zoster.

Immunosuppressant medication can theoretically increase the risk of malignancy related to decreased immune surveillance of pre-cancerous mutations. Patients on immunosuppression, especially TNF inhibitors and thiopurines, should have regular checkups for skin cancer and cervical cancer (in women). While the data are mixed, the current medications used for UC have not been consistently associated with an increased risk of solid tumors.

Other risks are less certain. For example, labels for TNF inhibitors such as adalimumab (Humira) include a , but this was based on slight increases seen in the clinical trials and on postmarketing case reports. A provided some additional support, finding a 36% increase in the odds of developing cancer with TNF inhibitors. An analysis of Swedish registry data showed no overall increase in cancers for TNF, JAK, or interleukin inhibitors. (Both analyses focused on patients with rheumatoid arthritis or related conditions, but most of the particular drugs involved are also used in UC.)

Next up: On the Horizon

Read previous installments in this Medical Journeys series:

Part 1: UC: Understanding the Epidemiology and Pathophysiology

Part 2: UC: Symptoms, Exams, Diagnosis

Part 3: UC: How and Why Does It Arise?

Part 4: Case Study: Why Is This Teen's Ulcerative Colitis So Severe, So Resistant?

Part 5: UC: Initial Treatments and Response Monitoring

Part 6: UC: Dietary and Lifestyle Interventions

Part 7: Ulcerative Colitis: Second-Line Treatments

Part 8: Case Study: Painful Distended Abdomen and Weight Loss -- What Is the Cause?

Part 9: Ulcerative Colitis: Helping Patients Live With Chronic Disease

Part 10: When Surgery Must Be Considered