Clinical Practice Guideline

for

CROHN’S DISEASE

Developed for the

Aerospace Medical Association

by their constituent organization

American Society of Aerospace Medicine Specialists

 

Overview: Crohn’s disease is a chronic, relapsing inflammatory condition of unknown etiology that can affect any portion of the gastrointestinal (GI) tract from mouth to perianal region.  It is manifested by a broad spectrum of clinical symptoms due to transmural involvement and the variability of the extent of disease.  Crohn’s disease and ulcerative colitis (UC) result from an aggregate effect of genetic and environmental factors leading ultimately to a state of perpetual and inappropriate activation of mucosal T cells, driven by the presence of normal enteric flora. The incidence of Crohn’s disease is 5 per 100,000 persons/yr and the prevalence is 50-90 per 100,000 persons.  Women have a slightly higher risk than men to develop Crohn’s disease with a peak age at onset between 15 and 25-30 years of age.  The absolute risk of Crohn’s disease is 5-8% among first-degree family members.  There is also a positive association with smoking, in contrast to UC, and with a diet high in refined sugar.  Discontinuous (“skip lesions”), transmural granulomatous inflammation of the GI tract is characteristic of Crohn’s disease.  Pathologic findings include a thickened and rubbery bowel wall with a narrowed lumen which can progress to strictures.  Noncaseating granulomas are characteristic but frequently absent.  Aphthous ulcerations of the bowel mucosa may progress to transverse and linear ulcers giving rise to a cobblestone appearance.  These linear ulcerations may deepen and fissure with transmural penetration leading to abscess and fistulae formation.

 

Clinically, Crohn’s disease is characterized by intermittent exacerbations of disease with interludes of remission.  Typical symptoms include diarrhea, colicky abdominal pain, weight loss, and a low-grade fever.  Signs and symptoms are dependent on the pattern and severity of disease.  The anatomic pattern of Crohn’s disease is as follows: one third have small bowel involvement only, 40-50% have ileocolitis (distal ileum and cecum), and 25% have disease confined to the colon only.  Thus, approximately 75% will have small bowel involvement.  Involvement of the upper GI tract is rare and almost always occurs with disease elsewhere.  Crohn’s can also be categorized by three general patterns independent of anatomic location:  fistulizing (perforating), fibrostenotic (stricturing) and inflammatory disease.  Extraintestinal symptoms can include reactive arthropathies, ankylosing spondylitis, eye involvement with uveitis and episcleritis, skin disorders of erythema nodosum and pyoderma gangrenosum, thromboembolism, and primary sclerosing cholangitis.  Malabsorption problems can lead to anemia, cholelithiasis, nephrolithiasis, vitamin deficiencies, and osteoporosis.  Patients with long-term active Crohn’s disease have an increased (but still rare) risk of small bowel adenocarcinomas, and in the case of longstanding Crohn’s colitis, an increased risk of colon cancer.

 

The diagnosis of Crohn’s disease is based upon a composite of endoscopic and/or contrast radiographic findings and compatible clinical correlation.  Colonoscopy is the procedure of choice for evaluation of the presence and extent of ileocolonic involvement.  Intestinal biopsy is confirmatory rather than diagnostic, and is usually nonspecific.  Approximately 10% of patients with colonic involvement alone will be diagnosed with indeterminate colitis when Crohn’s disease cannot be distinguished from UC.  Serologic markers (ANCA, p-ANCA, ASCA, and OMP-C, available as a panel from Prometheus Labs called IBD First Step™) can now be used to aid in diagnosis.

 

Treatment is aimed at restoring well-being and lifestyle and should be appropriately individualized.  Therapeutic recommendations depend upon anatomic location, severity, and complications.  Medical management is used to treat acute disease and for maintenance of remission, while surgical therapy is reserved for intestinal complications and medically intractable disease.  Although the mainstay of acute treatment continues to be the 5-aminosalicylate (5-ASA, mesalamine) compounds, maintenance therapy with 5-ASA is of questionable value in Crohn’s disease, unlike the situation with UC.  However, recent analyses of treatment trials do suggest some benefit for these drugs in preventing relapse of Crohn’s disease.   If 5-ASA therapy proves inadequate, antibiotics, or immunosuppressive drugs such as corticosteroids, 6-mercaptopurine, or anti-TNF therapy may be indicated.  Immunomodulating therapy has been shown to result in endoscopic healing, though unlike in UC, this is not the primary determinant of remission in Crohn’s.  The majority (80%) of patients will require surgical intervention, and of these, 50% will require subsequent surgery.  Post-operative disease recurrence is high with a 10-15% per year clinical recurrence rate.  After the initial episode, only 10-20% of patients have a prolonged remission.  Without therapy, 30% relapse within 1 year and 50% in two years. 

 

Aeromedical Concerns: It is important that we understand that Crohn’s disease is incurable.  Due to the frequency and nature of symptoms, as well as associated complications, Crohn’s disease should be considered disqualifying, and a special issuance is contingent upon the current status of the disease.  A major concern is that it is often a disease of younger people and it has an unpredictable course of remissions and exacerbations.  Even urgency and diarrhea may make flying distracting.  Problematic in the management of Crohn’s disease is the possible discrepancy between symptoms and objective signs of disease activity; intestinal obstruction can occur acutely in the apparent absence of disease activity.  Issues related to the aerospace environment include unpredictable fluctuating symptoms, abdominal pain, bowel obstruction, abscesses, chronic diarrhea, anemia, predilection to gallstones and kidney stones, GI perforation, and chronic medication usage with their inherent side effects.  All of the issues can lead to impairment secondary to pain and GI upset.

 

Anemia can predispose to hypoxia.  Hemoglobin of less than 10 grams is not allowed in civil aviation.  Effects of all medications must be considered, as many would interfere with safety of flight.  For example, the use of prednisone or equivalent in doses greater than 20 mg daily is not acceptable in civil aviation.  Extra-intestinal manifestations may also be cause for concern (kidney stones).  The long-term increased risk for carcinoma must be considered.  Abscesses occur in 15-20% of patients.  Fistulas occur in 20-40% of patients.  Gallstones occur in 25% of Crohn’s patients and their relative risk for gallstones is almost double compared with the general population.  Dose-related toxic effects of sulfasalazine include headache, nausea, vomiting.  Hypersensitivity reactions include rash, fever, aplastic anemia, agranulocytosis, hepatitis, pancreatitis, nephrotoxicity, pulmonary fibrosis and hemolysis.  Because most sulfasalazine toxicity is due to the sulfa component, time-pH release formulations of mesalamine (i.e., Pentasa, Asacol) are preferred.  Crohn’s disease confined strictly to the colon is less problematic from an aeromedical standpoint, and for waiver purposes is handled in a fashion similar to ulcerative colitis.

 

Medical Work-up: Internal medicine or general surgery consultation is recommended for initial waiver.  CBC results should also be reported.  Mention should be made of any associated illnesses and use of medications. 

 

Aeromedical Disposition (military and civilian): The disease should be stable, with no medications that would interfere with safety of flight.  Careful consideration of potential for incapacitation must be evidenced by appropriate consultation, and any change must be reported to the FAA or appropriate military service at once.  Every effort will be made to return aviators to flight when the disease is stable.  In general, cases requiring surgical resection are at high risk of recurrence.  Post-operative prophylaxis with a 5-ASA analog, which significantly decreases recurrence rates, should be considered.

 

Aviation personnel need to fulfill all of the following applicable qualifying criteria for waiver request (Crohn’s colitis refers to involvement of the colon alone, with no small bowel involvement):

 

General criteria (applies to military aviation, not civilian):

Crohn’s COLITIS

Crohn’s with SMALL BOWEL disease

Unrestricted waiver Pilot, Nav and other aircrew

Unrestricted Pilot

Pilot (categorical waiver*), non-pilots

·        No worse than mild disease (< 4 bowel movements/day)

·        Stable symptoms for three months

·        No fistulas,† strictures, abscess

·        Authorized medications include steroid enemas and/or topical (Rowasa) or oral (Pentasa, Asacol) aminosalicylates

·        Asymptomatic for 2 years

·        No fistulas,† strictures, abscess

·        No history of surgical resection

·        Authorized medications consist of oral (Pentasa, Asacol) aminosalicylates

·        Asymptomatic for 6 months

·        No fistulas,† strictures, abscess

·        No history of multiple surgical resections

·        Authorized medications consist of oral (Pentasa, Asacol) aminosalicylates

·        Any extraintestinal manifestation should be addressed as a separate diagnosis and will require individual work-up.

*Categorical waiver for Pilot: May operate only with another qualified pilot.

†Consideration for waiver may be given to cutaneous fistula only.

 

After a second exacerbation of Crohn’s with small bowel involvement, a categorical waiver may be considered after 12 months remission.  Crohn’s disease is disqualifying for initial military flying training; waiver is not recommended.

 

Since the implementation of AIMWTS, the waiver file reports 16 waiver requests for Crohn’s disease (ICD-9 559.XX) with 10 waivers granted (62.5%); of course, the denominator only consists of those considered candidates for waiver.  ACS experience with Crohn’s disease is limited and reveals 7 finalized cases with 3 receiving waiver recommendation (43%).

 

Waiver Experience (military): In one major military branch, there are 16 waiver requests for Crohn’s disease with 10 (62.5%) waivered.

 

Waiver Experience (civilian): For all classes of civil aviation, medical certification can be obtained.  Full recovery after any surgical treatment with favorable gastroenterologic consultation may be considered for certification.  Prophylactic medications and low dose prednisone (i.e. no more than 20 mg per day) are acceptable providing there are no adverse side effects.  Performance of airman duties is contraindicated for at least 12 hr after the use of diphenoxylate or loperamide.  As of calendar year 2006, the FAA has granted medical certification to 987 First Class, 809 Second Class, and 1,869 Third Class airmen.  This was for all forms of colitis.  For statistical purposes, at this time, the FAA does not distinguish between Crohn’s and ulcerative forms of colitis.

 

References:

 

1. Farrell RJ, Peppercorn MA.  “Medical management of Crohn’s disease.”  Peppercorn MA.  “Clinical manifestations and diagnosis of Crohn’s disease.”  Accessed from http://uptodateonline.com on 20 Jan 2005.

 

2. Feldman:  Sleisenger and Fordtran’s Gastrointestinal and Liver Disease, 7th ed. Elsevier, 2002 p. 2012-2028.

 

3. Friedman S.  General Principles of Medical Therapy of Inflammatory Bowel Disease.  Gastroenterol Clin N Am.  2004; 33:  191-208.

 

4. Judge TA, Lichtenstein GR.  Chap 7: Inflammatory Bowel Disease.  In: Friedman SL, ed.  Current Diagnosis & Treatment in Gastroenterology, 2nd ed.  New York: McGraw-Hill, 2003.

 

5. Kumar:  Robbins and Coltran’s Pathologic Basis of Disease, 7th ed. Elsevier, 2005.  p.847-849.

 

6. Lichtenstein GR, Cuffari C, et al.  Maintaining Remission Across the Lifespan:  A Roundtable Discussion with Crohn’s Disease Experts.  Inflamm Bowel Dis 2004; 10:  S11-S21.

 

7. Podolsky DK.  Inflammatory Bowel Disease.  N Engl J Med.  2002; 347:  417-429.

 

8. Shanahan F.  Crohn’s disease.  Lancet 2002; 359:  62-69.

 

9. Stenson, WF. Chap 142:  Inflammatory Bowel Disease.  In: Goldman, ed. Cecil Textbook of Medicine, 22nd ed.  W.B.  Saunders Co, 2004.

 

 

Updated: June 11, 2007