Patients with steroid-dependent Crohn's disease are those who respond to steroid therapy but cannot taper the treatment. Steroid-refractive patients are those who fail to respond to adequate treatment dosages of up to 1 mg per kg of prednisone within four weeks. Steroid dependency is common in patients with Crohn's disease who respond to prednisone treatment. Contributing factors associated with steroid dependency include cigarette smoking, nonsteroidal anti-inflammatory drug use, Clostridium difficile infection, and concurrent irritable bowel or chronic pain syndrome. Hanauer reviews the management of patients with steroid-dependent Crohn's disease.
Symptoms should be evaluated to rule out visceral hypersensitivity or malabsorption, which can masquerade as inflammatory disease. Initial investigation should include a complete blood count; determination of sedimentation rate or C-reactive protein level; and stool examination for leukocytes or lactoferrin, enteric pathogens, and C. difficile toxin. Radiographic studies or endoscopy may be useful for identifying fixed-stenoses, evidence of small bowel stasis, or short-segment disease. In patients with diarrhea, laxative abuse and other forms of surreptitious diarrhea should be excluded. Fecal fat analysis may reveal sensitivity to dietary fat intake.
Management strategies for steroid-dependent patients include surgery (if the patient has a short-segment disease, especially with evidence of stenosis) and immunomodulator therapy. Surgery potentially can restore health to a severely ill patient. Immunomodulator therapy with azathioprine or 6-mercapto-purine has been studied most frequently in combination with prednisone.Although combination therapy has some therapeutic advantage, the efficacy of these agents in steroid-dependent patients is unclear. Methotrexate and infliximab appear to be more successful in weaning patients from steroid dependence. Other agents such as mesalamine appear to have no use in tapering steroid-dependent patients.
The author concludes that patients with steroid-dependent Crohn's disease are best helped by reassessing the causes of the symptoms, eliminating potential exacerbating factors, employing surgery in select patients with localized disease, and using azathioprine or mercaptopurine. With the latter therapy, once patients are weaned from steroids, the purine antimetabolite is continued for an indefinite period while the physician monitors white blood cell count and liver enzymes. If purine metabolites cannot be used, methotrexate or infliximab can be tried. Patients who are refractory to steroids and immunomodulators and patients in whom steroids are contraindicated should be given infliximab for an indefinite period.
editor's note: Guidelines from the American College of Gastroenterology1 discuss the management of Crohn's disease in adults. Presenting symptoms of Crohn's disease can include chronic diarrhea, abdominal pain, intestinal obstruction, weight loss, fever, and night sweats. The differential diagnosis includes other inflammatory or idiopathic bowel disorders and irritable bowel syndrome. The impact of stress on symptoms is unclear. Disease activity is ranked depending on symptoms and the negative impact on a patient's quality of life. Therapy should consider treating the disease first and then keeping the patient in remission.
Patients with moderate to severe disease can be treated with prednisone in a dosage of 40 to 60 mg daily until symptoms resolve and weight gain resumes. Infliximab is a useful adjunct or alternative to corticosteroid therapy when the latter cannot be used or is ineffective. Because of the negative effects of chronic steroid use, an alternative agent should be used to maintain long-term remission. Azathioprine and mercaptopurine can be helpful after remission has been achieved with steroid therapy. In patients who have had ileocolonic resection, mesalamine, azathioprine, or mercaptopurine may help decrease the incidence of recurrence.—R.S.