Introduction
Concept of the second edition of consensus statements
|
According to increased use of anti-TNFα mAb in inflammatory bowel disease, many cases of intestinal Behçet’s disease in which anti-TNFα mAb (infliximab, IFX) showed efficacy also have been reported in Japan. The same tendency was observed in foreign countries that have a high prevalence of Behçet’s disease, such as Korea. In 2013, adalimumab, humanized anti-TNFα mAb was approved for intestinal Behçet’s disease in Japan. In the second edition, statements have focused on where we should place anti-TNFα mAb for the treatment of intestinal Behçet’s disease based on relevant literature and expert panel discussion.a
|
Diagnosis
|
1. Diagnosis of intestinal Behçet’s disease can be made if |
A. There is a typical oval-shaped large ulcer in the terminal ileum, OR |
B. There are ulcerations or inflammation in the small or large intestine, and clinical findings meet the diagnostic criteria of Behçet’s disease.b
|
2. Acute appendicitis, infectious enteritis, tuberculosis, Crohn’s disease, nonspecific colitis, drug-associated colitis and other diseases that mimic intestinal Behçet’s disease should be excluded by clinical findings, radiology, and endoscopy before diagnosis of intestinal Behçet’s disease is made. |
Assessment of severity
|
Disease severity should be comprehensively assessed by systemic symptoms (e.g., fever, extra-intestinal manifestations), physical examinations of abdomen (e.g., pain, inflammatory mass, rebound tenderness), depth of ulcers and intestinal complications (e.g., bleeding, stricture, fistula), inflammatory mediators (e.g., CRP, WBC, ESR), and anemia. |
Treatment objectives
|
In the treatment of intestinal Behçet’s disease, as well as the improvement of abdominal and extra-intestinal symptoms, the achievement of negative levels of CRP could be desirable. In the long-term prognosis, the prevention of progression to disability and poly-surgery is important. |
A. Standard treatment |
1. In patients with severe symptoms (i.e., abdominal pain, diarrhea, gastrointestinal bleeding) and complications with deep ulcers confirmed by radiology or endoscopy, corticosteroids should be considered for induction therapy. The initial dose of corticosteroids is 0.5–1 mg/kg per day of prednisolone for l–2 weeks. When clinical improvement is observed, prednisolone should be tapered by 5 mg every week and finally stopped. ADA (approved on May 16, 2013 in Japan) could be considered for induction therapy [160 mg at 0 w, 80 mg at 2 w, 40 mg at 4 w, sub-cutaneously (s.c.)]. In responders, scheduled maintenance therapy should be considered (40 mg s.c. every other week). IFX (not approved yet) could also be considered for induction therapy (5 mg/kg at week 0, 2, and 6). In responders, scheduled maintenance therapy every 8 weeks should be considered. In patients with mild to moderate activity, mesalasine (5-ASA) could be effective for induction therapy. In patients treated with corticosteroids, anti-TNFα mAbs and immunomodulators, infectious disease and neoplasm should be surveyed. After initiation of these therapies, the risk of infectious disease and neoplasm should be monitored continuously. |
2. In patients who are induced to clinical remission, 5-ASA and colchicine could be used for maintenance therapy. The optimal dose of 5-ASA for adult patients is 2.25–3 g/day. When sulfasalazine (SASP) is used, the optimal dose is 3–4 g/day. |
3. Immunosuppressive agents such as azathioprine (AZA)c are indicated when patients are corticosteroid-dependent, corticosteroid-resistant, or anti-TNFα mAb-resistant. The initial dose of AZA is 25–50 mg/day. In patients treated with AZA, adverse effects (e.g., neutropenia and liver dysfunction) should be monitored. |
4. Total parenteral nutrition (TPN) is indicated for patients with severe systemic symptoms such as fever and for patients with intestinal complications such as stenosis, fistula, bleeding, and impending perforation. TPN is also indicated for patients who cannot orally intake drugs due to severe oral or upper gastro intestinal lesions. It is usually used for a limited period of time considering the risk of catheter infection and thrombosis. After the patient’s condition is improved by TPN, enteral nutrition (EN) could be considered. |
5. EN using an elementary diet could be effective for induction therapy. It is indicated in particular for patients with refractory disease, severe activity, and disability such as stricture lesions. When EN is introduced, adherence and quality of life of the patients should be considered. |
6. Surgery is indicated for patients in whom improvement is not expected by medications. Patients with severe stricture lesions, perforations, large abscesses, and massive gastrointestinal bleedings have an absolute indication. Patients refractory to medications, and with a low quality of life due to intestinal complications such as fistula, have a relative indication of surgery. Minimum length of resection surgery should be considered. |
7. Risk of post-operative recurrence is high in patients with volcano shape deep ulcers and fistulas. Post-operative recurrence often occurs at anastomosis. Although a treatment strategy has not been established that can reduce the risk of post-operative recurrence, considering the high risk of post-operative recurrence and poly surgeries, medication by 5-ASA, immunomodulators, metronidazole, anti-TNFα mAb and EN could be considered for post-operative management. |
8. In patients with intestinal Behçet’s disease complicated with eye lesions, consultation with ophthalmologists is necessary for their management |
B. Optional treatment |
• Since there are some case reports showing that spraying of absolute ethanol via endoscope has efficacy for ulcers of intestinal Behçet’s, it could be considered in refractory patients. |
• Expecting the efficacy as an anti-rheumatoid arthritis drug, change from 5-ASA to SASP could be considered in patients with arthritis (especially peripheral arthritis). |