Max: a case study for steroid-dependent ulcerative colitis
Professor Gibson presented the case of ‘Max’, a 29-year-old, unmarried information technology expert who had never smoked and had a low-to-moderate alcohol intake. (Identifying details of both cases discussed at the meeting have been changed to ensure their anonymity).
4:25 – Role of intestinal ultrasound
13:30 – Management of relapsing ulcerative colitis
22:44 – Accessing REMICADE on the PBS for moderate-to-severe ulcerative colitis
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Max was diagnosed with UC in 2006. He had bloody diarrhoea and extensive confluent disease on colonoscopy, with histopathology consistent with pan-ulcerative colitis. Max was treated successfully with oral prednisolone, and remission was maintained with mesalazine 3 g/day. He commenced azathioprine 50 mg/day but ceased because of nausea.
Max presented in February 2013 at a different centre with a flare of bloody diarrhoea, which responded to IV corticosteroids. The patient provided little information about his prior history, treatments received and his attitude to investigations and maintenance therapy. He commenced mercaptopurine 50 mg/day, but ceased after 6 months because he perceived it as providing no benefit. He agreed to a colonoscopy in October 2013, which showed mildly-active distal colitis.
Another flare was treated with oral prednisolone and a topical corticosteroid, aiming for a slow wean of prednisolone over 3–4 months because of his history of relapses. Mesalazine was commenced at 3 g/day.
Max was admitted to hospital because of another flare. He was treated with IV corticosteroids, mercaptopurine 50 mg/day was commenced, and mesalazine increased to 4 g/day. Flexible sigmoidoscopy showed confluent moderate colitis to 50 cm and biopsies showed moderate UC with no CMV infection. Oral prednisolone was commenced. The episode further confirmed a pattern of recurrent steroid-responsive disease.
On review in the clinic in September, Max reported normal bowel actions without blood or urgency. Oral prednisolone was still being tapered, and mercaptopurine was escalated as planned to 75 mg/day towards a target of 100 mg/day (Max weighed 80 kg). Intestinal ultrasound showed evidence of mild disease in the descending colon with slight thickening and increase in the Doppler signal suggesting excessive circulation. The ascending colon, caecum and terminal ileum were normal, with normal motility.
Increasing mercaptopurine to 100 mg/day in October led to nausea, but Max persisted with the medication. The 6TGN level was 564 pmol/8×108 RBC, and the 6-MMP level
3607 pmol/8×108 (ratio 6.4), indicating an adequate to high therapeutic level and absence of shunting.
Breakthrough symptoms occurred when prednisolone was reduced to 5 mg/day. He was treated by increasing the dose to 15 mg/day and with mesalazine enemas. Low-grade symptoms persisted throughout November, including 2–3 bowel actions per day that were formed but had some blood, and continuing nausea associated with mercaptopurine.
Summary and treatment options
“This patient has steroid-responsive, but steroid-dependent, ulcerative colitis,” Professor Gibson said. “He is unable to achieve remission without steroids, and had an inadequate response to 10 weeks treatment with mercaptopurine at 100 mg/day. Therapeutic options at this stage may include methotrexate (but there is only low quality evidence for efficacy in UC), further optimisation of mercaptopurine, commencement of infliximab, or tacrolimus enemas for distal disease. Perhaps the possible benefits of colectomy should also be discussed.”
Max was treated with an induction course of infliximab, consisting of three doses at 5 mg/kg administered at weeks 0, 2 and 6.
The following points arose during discussion of the case by the expert panel and comments by attendees:
- At least 10% of patients who appear clinically to have UC may have Crohn’s disease.1 Investigation of the small bowel is often recommended to confirm the diagnosis but the implications for treatment are uncertain, other than the possibility of adding methotrexate to the therapeutic options and influencing the potential role of surgery.
- The panel and other meeting participants noted that, in experienced hands, ultrasound can be sufficient to exclude Crohn’s disease. The sensitivity is probably lower than for ileoscopy, but it is improving and is now comparable to MRI and CT. Ultrasound is safe, non-invasive and simple to repeat if needed. For a review of the radiological evaluation of UC, see Deepak et al (2014).2
- Max requires a full surveillance colonoscopy and comprehensive biopsies to check for dysplasia, as he has had UC for at least 8 years. It was suspected he had resisted previous advice to have colonoscopy.
- Max could be described as having ‘under-treated’ UC. There appears to have been little attempt to optimise immunomodulator therapy, he commenced on low doses of 5-ASA, and has now required two hospital admissions. However, ‘under-treatment’ is easier to define in retrospect than in the present, as past management reflects patients’ preferences, choices and circumstances as well as the medical advice that they receive.
- This case reinforces the fact that initial extensive disease is a predictor of poor outcomes in UC. Panel members estimated that only about 20% of patients with UC ever require hospital admission for IV corticosteroids, and Max has required this twice. Extensive disease, therefore, suggests a need for an assertive approach to early treatment and follow-up.
- Panel members stated that when IV corticosteroids are required for flares, they should be given at effective doses, for example 40 mg/kg, rather than as small incremental increases of pre-existing oral doses.