Clinical Practice Guideline
Developed for the
Aerospace Medical Association
by their constituent organization
Overview: Ulcerative colitis (UC) is a chronic, relapsing inflammatory condition of unknown etiology affecting the mucosal layer of the colon. Inflammatory bowel disease (IBD), which includes UC and Crohn’s disease, is a chronic condition resulting from inappropriate mucosal immune activation. The most important risk factor is a positive family history for IBD; approximately 15% of IBD patients have affected first-degree relatives. Dr. Samuel Wilks is credited with being the first to describe UC as a distinct entity from bacillary dysentery in 1859. The hallmark clinical symptom is bloody diarrhea often with prominent symptoms of rectal urgency and tenesmus. UC affects approximately 500,000 people in the United States with an incidence of 8-12/100,000/year (no gender difference) and this incidence has been relatively constant over the past five decades.
The clinical presentation is dependent on the extent of colonic involvement and severity of disease. UC invariably begins with inflammation of the rectum and spreads continuously and proximally for variable distances. Disease restricted to the rectum is referred to as ulcerative proctitis (confined to rectum; generally distal 25 cm); left sided colitis is that confined from the distal to splenic flexure, pancolitis is the term to define disease that includes the proximal colon to the splenic flexure; universal colitis is that involving the entire colon, including the cecum; and backwash ileitis is inflammation of distal 10cm or less of terminal ileum in the setting of universal colitis.
UC has a variable degree of presentation. Mild disease is almost always confined to the distal colon and rectum and is associated with intermittent rectal bleeding and mild diarrhea consisting of fewer than four small loose stools per day. Moderate disease normally involves more than the distal colon with disease at least to the splenic flexure. There are frequent loose, bloody stools (up to 10/day) with mild anemia not requiring transfusion, abdominal pain not classified as severe, and possibly with low grade fever. Patients with severe disease have extensive colonic disease, frequent loose stools (more than 10/day), with severe cramps, fever up to 39.5o C, and bleeding often severe enough to require transfusion.
Assessment of disease severity stems from patient complaints (number of bowel movements, presence of blood per rectum, abdominal pain), the impact of disease on daily activities, pertinent physical exam findings, and the presence of abnormal laboratory tests. About 60% of patients have mild disease (mild diarrheal symptoms and no systemic involvement); however, almost all patients have at least one relapse during a 10-year period, and 25% will require colectomy within 3 years of onset for uncontrollable disease. Extraintestinal symptoms can include reactive arthropathies, ankylosing spondylitis, eye involvement with uveitis and episcleritis, skin disorders of erythema nodosum and pyoderma gangrenosum, thromboembolism, autoimmune hemolytic anemia, and primary sclerosing cholangitis. Local complications of UC include massive hemorrhage, fulminant colitis, intestinal perforation and stricture or toxic megacolon (both rare). Despite the burden of a chronic illness, more than 90% of UC patients are able to maintain capacity for work after 10 years of disease and the overall quality of life is not impaired significantly.
The most feared long-term complication is colorectal cancer. Patients with extensive ulcerative colitis have a markedly increased risk for colon cancer in comparison to the general population beginning 8 to 10 years after diagnosis and increasing with time. The usual figure is 4 – 5 times that of the general population and it increases by a factor of 50 for those who also have primary sclerosing cholangitis complicating their UC. The risk for malignancy is also a function of the anatomic extent of the disease; the risk is much greater with pancolitis than with left-sided disease. Patients with long-standing ulcerative colitis are at risk for cancer even if their symptoms have been relatively mild; that is, colon cancer is seen in patients whose disease has been quiescent for 10 to 15 years. In ulcerative colitis, colon cancers are frequently submucosal and may be missed at colonoscopy. Colon cancer in patients with ulcerative colitis is associated with dysplastic changes in the mucosa at other sites in the colon. Dysplasia cannot always be identified by visual inspection; microscopic examination of biopsy specimens is required. The current standard of care is to perform surveillance colonoscopy with random biopsies in patients with long-standing ulcerative colitis beginning 8 to 10 years after the onset of disease and repeated every 1 to 2 years. If the specimens show dysplasia, the patient is sent for colectomy. Although it is clear that dysplasia is associated with colon cancer in patients with ulcerative colitis, the utility of surveillance colonoscopy has not been firmly established.
Pathologic findings include mucosal erythema, edema, granularity and erosions. With more severe disease, there are ulcerations, erosions with adherent mucopus, friability and hemorrhage. The characteristic histopathology is crypt architectural distortion and gland drop-out. A lymphoplasmocytic infiltrate is also generally seen. Peak age of onset is between 15 and 30 years of age. Compared to current smokers, non-smokers and former smokers are at increased risk for UC. The diagnosis of UC is made by exclusion of other causes of diarrhea (in particular, infectious etiologies) and a characteristic history with corresponding mucosal findings on endoscopy. Histology of biopsies may confirm the diagnosis.
Medical management is used to treat acute disease and for maintenance of remission. The mainstay of treatment is 5-aminosalicylic acid (5-ASA, or mesalamine), administered either topically (when disease is limited to the distal colon) or orally (which requires some mechanism to bypass the upper intestine). The prototypical agent was sulfasalazine (Azulfidine®), which consists of 5-ASA conjugated with a sulfa moiety; the bond between the two moieties was lysed in the colon, and both were believed to be active. However, it is now understood that efficacy of sulfasalazine in UC is due to 5-ASA, while most of its toxicity was due to the sulfa moiety. Currently, oral mesalamine coated in a manner that delays intestinal release (e.g., Pentasa®, Asacol®) is much preferred. (Sulfasalazine was originally developed, and is modestly effective, for the treatment of rheumatoid arthritis, a condition for which, pure mesalamine compounds are curiously ineffective.) When salicylate therapy alone is inadequate for achieving control of UC, corticosteroids, antibiotics, or immunosuppressive drugs (azathioprine, 6-mercaptopurine [6-MP], cyclosporine, methotrexate) may be indicated. Individuals who have reached remission should remain on maintenance therapy with aminosalicylates, which are proven to substantially reduce the incidence of relapse; evidence is also mounting that they offer a protective effect against colorectal cancer. The extent of disease can be predictive of the disease progression and prognosis, with pancolitis leading to more severe attacks than limited disease. Remission in UC is generally tied to the patient’s change in symptomatology with therapy.
The role of tumor necrosis factor inhibitors in uncontrolled UC is a subject of great interest, with infliximab showing benefit. Infliximab (Remicade®) has been studied extensively and has been shown to be an effective therapy for moderate to severe cases of UC. Aviators treated with infliximab need to be observed for at least six months on the medication before consideration of waiver to allow for assessment of response and possible adverse affects.
Removal of the colon and rectum cures ulcerative colitis. Indications for surgery include medically refractive disease, intractable disease with an impaired quality of life, unacceptable side effects from medications, uncontrolled hemorrhage, toxic megacolon perforation, and development of dysplasia or cancer. There are no prospective randomized trials comparing medical treatment of UC to surgery for any indication, but the three absolute indications for surgery are exsanguinating hemorrhage, frank perforation, and documented carcinoma.
The most common surgery is restorative proctocolectomy with ileal pouch anal anastomosis (IPAA), which consists of removal of the entire colon and rectum with preservation of the anal sphincters, and construction of a pouch from approximately 20 cm of the distal ileum. An IPAA is usually performed as a two-stage operation, with the first stage including creation of a temporary diverting ileostomy to allow the ileal pouch to heal. Mean stool frequency ranges from 4 to 9 bowel movements per day, including 1 or 2 nocturnal stools. Rates of complications vary and include obstruction, sepsis, abscess, anastomotic leak, fecal incontinence and sexual and urinary dysfunction. Pouchitis, a nonspecific inflammation of the ileal reservoir, is the most common long-term complication of colectomy with IPAA. Symptoms are similar to UC, with increased frequency of defecation, rectal bleeding, abdominal cramping, rectal urgency, tenesmus and fecal incontinence. Pouchitis occurs in about 20% of individuals, with the highest incidence during the first 6 months after closure of the temporary loop ileostomy. Primary treatment is with antibiotics, with topical and oral mesalamine as second-line therapy.
Aeromedical Concerns: Aeromedical disposition of UC is considerably simpler than Crohn’s disease; major complications are unusual and rarely of sudden onset. If an aviator is grounded, it is more often due to the impracticality of flying with frequent bowel movements. Ulcerative proctitis by itself tends to be mild, and is often controllable by aminosalicylate or steroid enemas. With colitis, there is a minimal risk for subtle performance decrement due to gradual onset of anemia if occult blood loss occurs. Relapse is heralded by typical symptoms of diarrhea and can be accompanied by rectal bleeding, fever and malaise in more severe cases. Relapses can also be triggered by psychological stress. However, the aminosalicylates have proven effective to sustain remission and reduce relapse. Dose-related toxic effects of sulfasalazine include headache, nausea, and vomiting. Hypersensitivity reactions include rash, fever, aplastic anemia, agranulocytosis, hepatitis, pancreatitis, nephrotoxicity, pulmonary fibrosis and hemolysis. Although delayed-release forms of mesalamine (e.g., Asacol®, Pentasa®) are more costly than sulfasalazine, these agents are preferred to minimize adverse effects. Immunosuppressants (except etanercept and infliximab), oral steroids and biological agents are not approved for flying duties due to many adverse systemic effects. Although etanercept has been approved for waiver in inflammatory arthropathies and psoriasis, it is not effective in the treatment of ulcerative colitis. Infliximab has been shown to be efficacious in the treatment of ulcerative colitis.
Medical Work-up: Medical evaluation of an aviator with the diagnosis of ulcerative colitis should contain a complete history that include the disease course (gastrointestinal symptoms), current therapy, presence of complications and surgical resection, presence or absence of any symptoms suggesting extraintestinal disease (e.g. uveitis, arthritis, ankylosing spondylitis, thromboembolism, primary sclerosing cholangitis, skin disease). Lab test should include a complete blood count (CBC), ESR, LFTs, C-reactive protein (CRP), and albumin. Also necessary is the result of the colonoscopy with mucosal biopsy results. Finally, a consultation report from internal medicine or gastroenterology is very useful.
Air Force: UC and ulcerative proctitis are disqualifying for all flying classes. Waiver is not recommended for FC I/IA and untrained FC II and FC III individuals. Any extraintestinal manifestations of UC should be addressed as separate diagnoses and will require individual work-up. (See venous thromboembolic disease, primary sclerosing cholangitis, and ankylosing spondylitis waiver guides.) If a course of oral steroids of greater than three weeks duration is required to achieve control, but is followed by maintenance of remission on waiverable medications, waiver could be considered after the pituitary axis has returned to normal function (based on Cortrosyn® stimulation testing; see waiver guide – systemic glucocorticoid (steroid) treatment).
Ulcerative colitis is not mentioned by name for FC IIU personnel, but GI bleeding and diarrhea of sufficient severity to require frequent interventions or to interfere with normal functioning is disqualifying. For ATC/GBC personnel, the important consideration is for gastrointestinal bleeding. Regarding SMOD personnel, there are no listed disqualifications that pertain to ulcerative colitis, gastrointestinal bleeding, or diarrhea.
Ulcerative colitis is disqualifying for retention standards in the Air Force. The flight surgeon needs to be aware that an MEB will also be required as part of the overall care, although the two are separate processes.
Army: Ulcerative Colitis is disqualifying for aircrew of all classes. Army policy is articulated in the APL of the same name. Army concerns are well reflected in this CPG. The work-up requires a GI evaluation and colonoscopy. Sulfasalazine in doses up to 2 gm/day or mesalamine in doses up to 2.4 gm/day or 6 gm/day, have been waivered for maintenance therapy. Higher doses may be required for treatment, but are not recommended for waivers. Steroid and 5-aminosalicylic acid (5-ASA) enemas have been approved for treatment of proctitis. Partial colectomy is a viable alternative in Army aircrew that cannot tolerate medication or are unmanageable with medical therapy. However, with pancolitis and/or the appearance of high-grade dysplasia or colon cancer, total colectomy with sparing of the rectal musculature for an eventual continency procedure is the preferred operation. A waiver is very rarely if ever granted for any flight training applicant. In rated aircrew, waivers may be considered if disease is classified as mild, left-sided, in remission for at least 1 month, and limited to the distal 25 cm of the colon. If the disease is treated by partial colectomy, a waiver recommendation can be made 1 year after surgery, provided the patient is asymptomatic and is without a colostomy or ileostomy.
Navy: Applicants with Ulcerative Colitis are Considered Disqualified (CD), no waiver. Restricted waivers are possible for designated aircrew, but are reserved for mild cases in remission for at least one month. The only waiverable maintenance medications are sulfasalazine (max 2 grams/d), Asacol (up to 2.4 grams daily), and/or steroid enemas. Higher doses may be required for treatment, but are not recommended for waivers. All other pharmacologic therapy, except for dietary adjuncts such as folic acid, is CD. If the disease is treated by partial colectomy, a waiver recommendation can be made one year after surgery, provided the patient is asymptomatic. All patients requiring surgery for control of the disease must have a PEB finding them fit for full duty before waiver recommendation will be considered. Surgical therapy resulting in a permanent colostomy or ileostomy is CD, no waiver.
1. Internal medicine or gastroenterology consultation
2. Recent sigmoidoscopy or colonoscopy
3. Documentation of the extent of the disease process
FOLLOW-UP: Annual submission is required with gastroenterology consultation including flexible sigmoidoscopy/colonoscopy report. The appropriate specialist must evaluate joint or ophthalmologic symptoms.
Civilian: Ulcerative colitis is disqualifying for all classes of medical certification. It requires the airman to demonstrate that the condition is under control. If the airman has an acute exacerbation, they are told to ground themselves. The associated medical conditions, such as Primary Sclerosing Cholangitis, also will require an authorization for special issuance. Currently, the one treatment situation that is not acceptable is when doses of steroids equivalent to prednisone over 20 mg are prescribed. This generally occurs in an acute exacerbation.
Air Force: AIMWTS review revealed a total of 117 cases with the diagnosis of ulcerative colitis. There were 0 FC I/IA cases, 78 FC II cases, 24 FC III cases, 1 FC IIU case, 3 ATC/GBC cases, and 11 SMOD cases. Of this total, 18 were disqualified: 6 were FC II, 8 FC III, 1 FC IIU, 2 ATC/GBC, and 1 SMOD. Most of the disqualifications were due to issues related to the UC diagnosis.
Army: Ulcerative colitis is a relatively uncommon diagnosis among rated Army aviators. Between 2009 and 2011 there was an average rated aviator population of 14919 in any given year as identified by having an annual flight physical. During this period, there was an average of 3.67 cases carrying the diagnosis of ulcerative colitis in any given study year, yielding an average one year period prevalence of 2.46 cases per 10,000 aircrew. There were 5 applicants for aviation training with UC one of which was granted a waiver for minimal disease. Also, during this 3 year period there were 10 cases in the rated population of which 2 were suspended and 8 granted waivers.
Navy: Not available at this time
Civilian: There are currently 751 first-, 460 second-, and 1,519 third-class airmen issued with ulcerative colitis. Due to coding issues at the FAA, these figures may include ulcerative colitis , Crohn’s disease, and airmen with a diagnosis of nonspecific colitis.
ICD 9 code(s) for ulcerative colitis
Ulcerative colitis, unspecified
Turner JR. The Gastrointestinal Tract. Ch. 17 in Kumar: Robbins and Cotran Pathologic Basis of Disease, 8th ed., Saunders, 2009.
Stenson WF. Inflammatory bowel disease. Ch. 144 in: Goldman: Cecil Textbook of Medicine, 23rd ed., Saunders, 2007.
Osterman MT and Lichtenstein GR. Ulcerative Colitis. Ch. 112 in Feldman: Sleisenger and Fordtran’s Gastrointestinal and Liver Disease, 9th ed., Saunders, 2010.
Langan RC, Gotsch PB, Krafczyk MA, and Skillinge DD. Ulcerative Colitis: Diagnosis and Treatment. Am Fam Physician, 2007; 76:1324-30.
Kornbluth A, Sachar DB, et al. Ulcerative Colitis Practice Guidelines in Adults: American College of Gastroenterology, Practice Parameters Committee. Am J Gastroenterol, 2010; 105:501-23.
Peppercorn MA. Clinical manifestations, diagnosis, and prognosis of ulcerative colitis in adults. UpToDate. Online version 18.1, Jan, 2010.
Metcalf AM. Elective and Emergent Operative Management of Ulcerative Colitis. Surg Clin N Am, 2007; 87:633-41.
Abraham C and Cho JH. Inflammatory Bowel Disease. N Engl J Med, 2009; 361:2066-78.
Peppercorn MA and Farrell RJ. Medical management of ulcerative colitis. Online version 18.1, Jan, 2010.
Rutgeerts P, Sandborn WJ, Feagan BG, et al. Infliximab for Induction and Maintenance Therapy for Ulcerative Colitis. N Engl J Med, 2005; 353:2464-76.
Pickard JS. Background paper for AFMOA/SGPA on Infliximab, Aug 2009.
Prepared by Dr. Dan Van Syoc
May 21, 2012