A 35-year-old woman is evaluated for symptomatic ulcerative colitis. One year ago, she was diagnosed with pan-ulcerative colitis and responded well to initial and maintenance therapy with balsalazide. However, 2 months ago she developed urgent bloody diarrhea several times a day and lower abdominal cramping; prednisone, 40 mg/d, alleviated her acute symptoms, but her symptoms have returned with prednisone tapering. The patient is otherwise healthy, and her medications are balsalazide, 750 mg three times a day, prednisone, 15 mg/d, and calcium with vitamin D.
On physical examination, vital signs and other findings are normal. Laboratory studies reveal hemoglobin 11.4 g/dL (114 g/L) and plasma glucose 140 mg/dL (7.77 mmol/L). Stool analysis for Clostridium difficile toxin A and B is negative.
Which of the following is the most appropriate next step in the treatment of this patient?
Answer and Critique (Correct Answer: D)
Educational Objective:Treat ulcerative colitis.
- Patients with ulcerative colitis who become corticosteroid-dependent should be started on therapy with an immunomodulator, such as azathioprine or 6-mercaptopurine with a steroid taper.
5-Aminosalicylates (5-ASA) are the first-line therapy for ulcerative colitis, and remission can often be induced and maintained with a 5-ASA only. When 5-ASA therapy is not effective initially or patients develop a flare while in remission on 5-ASAs, often a short course of corticosteroids is required to induce or re-induce remission. However, corticosteroids are not effective as maintenance therapy and have many potential side effects, including hyperglycemia, osteoporosis, hypertension, mood instability, acne, infection, and osteonecrosis. Although some patients may maintain remission with continued 5-ASA therapy after corticosteroid taper, other patients become corticosteroid-dependent or -resistant, as did this patient, and therapy with an immunomodulator such as 6-mercaptopurine or azathioprine should be started. These agents are nucleotide analogues that interfere with DNA synthesis and induce apoptosis. Therapy with these agents may be required for up to 3 months before providing clinical benefit, and therefore, they are generally started with corticosteroids, which are then tapered.
Because corticosteroids are not effective maintenance therapy, simply increasing the dose of prednisone without adding an immunomodulator would not be appropriate in this patient. The addition of another 5-ASA, such as olsalazine, will not provide any greater benefit. Antibiotic therapy has not been shown to be effective in the treatment of ulcerative colitis, and the patient’s stool was negative for Clostridium difficile. Budesonide is a nonsystemic corticosteroid that is useful in the induction of remission in patients with ulcerative colitis disease involving the terminal ileum and right colon, but would not be of added benefit in this patient with pan-ulcerative colitis.
- Baumgart DC, Sandborn WJ. Inflammatory bowel disease: clinical aspects and established and evolving therapies. Lancet. 2007;369 (9573):1641-1657. [PMID:17499606] - See PubMed
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