Case: 24-Year-Old Woman With Ileal CD and Perianal Fistula
History and presentation. Megan is a 24-year-old woman who was referred for consultation on the management of her ileal CD, which was diagnosed at age 19 years. It has been managed with mesalamine (two 500-mg capsules 4 times daily), and oral prednisone has been used for flares. When her disease flares, prednisone helps Megan’s diarrhea and abdominal pain, but she has needed two to three 4-week courses each year.
Eight weeks ago, she developed a perianal enterocutaneous fistula, with small volume drainage of a purulent material and occasional blood, and experienced increasing abdominal pain and diarrhea. She was treated with oral prednisone 20 mg/d. Her symptoms improved at this dosage but increased whenever the prednisone was tapered below 15 mg/d. Currently, she has 5 to 6 loose stools daily with occasional nocturnal stooling. She has right lower quadrant (RLQ) and left lower quadrant (LLQ) abdominal pain, which increases 1 to 2 hours after eating. Her appetite has decreased, despite continued treatment with prednisone, and she has lost 6 lb during the past 2 months. She reports having no recent fevers or chills and no arthralgias.
Megan recently completed graduate school, is married, and hopes to start a family soon. Her clinician has mentioned immunomodulators and biologic agents, but Megan is concerned about the effects of these drugs on a future pregnancy. She is also concerned about the long-term use of these agents and the risk of possible malignancy. She is a nonsmoker and has no known drug allergies. In addition to mesalamine and prednisone, she takes a multivitamin daily.
Physical findings. General appearance: thin, in no acute distress; head, eyes, ears, nose, throat (HEENT): conjunctiva pink, buccal mucosa with a few aphthous ulcers; neck supple without adenopathy; lungs: clear to auscultation; heart: regular rate and rhythm, without murmur or gallop; abdomen: normal bowel sounds, no organomegaly to percussion, soft with increasing tenderness from RLQ to LLQ, and a palpable fullness in the RLQ but without guarding; perianal inspection: no erythema, a 2-mm left posterior-lateral fistula ~ 2 cm from the anus, no induration but mild tenderness, a small volume of purulent material expressed; extremities: no clubbing, cyanosis, or edema; skin: no rash.
Laboratory findings. White blood cell count: 10,800/µL; hemoglobin: 11.6 g/dL; hematocrit: 33%; platelet count: 410,000/µL; complete metabolic profile: within normal limits; C-reactive protein (CRP): elevated at 16 mg/L.
Computed tomographic (CT) enterography findings. Distal ileal inflammation with 2+ mucosal enhancement and decreased luminal diameter in 2 segments: one of 10- to 12-cm length and another more proximally of 4- to 5-cm length; no prestenotic dilation; mesenteric stranding noted in the RLQ of the abdomen; mild thickening of the rectum but without pelvic fluid collection or abscess.
Endoscopic findings. Inflammation of the ileocecal valve; terminal ileum could not be intubated, but biopsy samples were obtained; colon otherwise normal, except for mild rectosigmoid erythema; small perianal fistula.
Biopsy findings. Terminal ileum: moderate inflammation (acute and chronic) but without granulomas; cecum and right colon: mild chronic inflammation; transverse and descending colon: normal mucosa; rectosigmoid colon: mild inflammation.
How would you manage this patient?
Dr Hanauer and Mr Davis offer expert commentary on treatment options.
Dr Hanauer: CD is a chronic disorder requiring 2 phases of treatment: induction of remission and maintenance of remission. This patient is still ill and requires both an induction and maintenance plan. Several approaches are possible. If her CD responds to steroids, a thiopurine can be added to maintain remission as the steroids are withdrawn. She already has had several courses of steroids. If she has contraindications to continued steroid use, the combination of a biologic with a thiopurine would provide the best long-term approach to treatment. If steroids are able to induce remission but thiopurine therapy is not able to maintain remission successfully, the introduction of a biologic concomitantly with the thiopurine has been demonstrated to be effective for both induction and maintenance. One question that remains to be addressed by clinical trials is what to do on a long-term basis once a patient has responded to combination therapy with a biologic and an immunosuppressant. It appears that either agent may be stopped after 1 year as long as the patient’s disease is in a deep remission with mucosal healing. If the patient continues to improve but has residual evidence of active inflammation at endoscopy or by laboratory findings (eg, elevated CRP), continuation of combination therapy will be required.
Mr Davis: Mesalamine should be discontinued because it likely is of minimal benefit in this patient. One option would be to initiate immunomodulatory treatment with 6-MP or AZA. Bridge therapy with antibiotics and budesonide could be used until a therapeutic response is achieved. Measuring TPMT activity before starting thiopurine therapy should be considered. Thiopurine metabolites could be measured at weeks 4 to 6, and the dosing accelerated if needed. Because Megan wants to start a family, MTX, which has teratogenic effects, should be avoided.
Another management approach to consider is biologic therapy with an anti-TNF agent (adalimumab, certolizumab, or infliximab) and tapering of the corticosteroid. Options (ie, intravenous [IV] agent [infliximab] vs self-injectable agents [adalimumab or certolizumab]) should be discussed with the patient. The option of future surgery could also be discussed; however, because Megan has segmental ileal disease and a perianal fistula, medical therapies should be explored first. A fistulogram and/or exploration of the fistula with a probe could be considered to confirm the presence of a fistula and not an abscess with a sinus tract.
It is important to educate the patient about the risks of undertreating CD, including the risk active disease poses to pregnancy.67 These risks should be weighed against the benefits and risks associated with the use of immunomodulatory or biologic agents.