Contributors to the development of the guidelines
-
Fumiaki Ueno (Chair); Ofuna Chuo Hospital,
-
Takayuki Matsumoto (Vice-chair); Division of Lower Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine,
-
Hiroaki Ito; Kinshukai Infusion Clinic,
-
Nagamu Inoue; Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine,
-
Kiyonori Kobayashi; Department of Gastroenterology, Kitasato University East Hospital,
-
Kenji Kobayashi; Division of Endoscopy, Ofuna Chuo Hospital,
-
Akira Sugita; Department of Surgery, Yokohama Municipal Citizen’s Hospital,
-
Yasuo Suzuki; Department of Internal Medicine, Toho University Medical-Center Sakura Hospital,
-
Yoshinori Noguchi; Department of General Internal Medicine, Nagoya Daini Red Cross Hospital,
-
Toshiaki Watanabe; Department of Surgery, The University of Tokyo School of Medicine
-
Toshiyuki Matsui (Chair); Department of Gastroenterology, Fukuoka University Chikushi Hospital,
-
Mamoru Watanabe (Vice-chair); Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University,
-
Ryosuke Shoda; Departments of Internal Medicine and General Clinical Practice, East Saitama National Hospital; Nobuo Hiwatashi, Iwaki Kyoritsu General Hospital,
-
Seiji Bito; Division of Clinical Epidemiology, National Hospital Organization Tokyo Medical Center
-
Mamoru Watanabe (Principal investigator); Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University
-
Toshifumi Hibi (Responsible trustee); Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine,
-
Kentaro Sugano (Chair, Supervision Committee); Department of Gastroenterology, Jichi Medical University Hospital,
-
Takeo Nakayama (Adviser); Department of Health Informatics, Kyoto University,
-
Naohiko Yamaguchi (Literature searcher); Toho University Media Center
-
Toshifumi Hibi; Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine,
-
Katsuyoshi Matsuoka; Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine,
-
Fumiaki Ueno; Ofuna Chuo Hospital
Introduction
I | Systematic review/Meta-analysis of randomized controlled trials |
II | Based on one or more randomized controlled trials |
III | Based on a non-randomized controlled trial |
IVa | Analytical epidemiological study (cohort study) |
IVb | Analytical epidemiological study (case–control study or cross-sectional study) |
V | Descriptive study (case report or case series) |
VI | Opinion of an expert committee, or an expert, not based on patient data |
Level of evidence | Consensus (median value of Delphi evaluation) | |||
---|---|---|---|---|
8 or more | 7 | 6–4 | 3 or less | |
I | A | A | C2 | D |
II | A | B | C2 | D |
III | B | B | C2 | D |
IV | B | C1 | C2 | D |
V | C1 (B*) | C1 | C2 | D |
VI | C1 (B*) | C1 | C2 | D |
A | Strong recommendation, with high level of evidence |
B | Moderate recommendation, with certain level of evidence |
Supported by an intermediate level of evidence and considered to be clinically useful | |
Supported by a high level of evidence but not considered to be clinically very useful | |
Evidence level is low, but usefulness has already been established in clinical practice | |
C1 | Recommendation to be done, without a high level of evidence |
C2 | Recommendation not to be done, without a high level of evidence |
D | Recommendation not to be done, as evidence indicates ineffectiveness or harm |
Disclosure of conflicts of interest
Medical professional contracts with the following companies:
|
Ajinomoto, Astellas, Abbott, Eisai, LTT Bio-Pharma, Otsuka, Kyorin, Zeria, Mitsubishi Tanabe, Chugai, FUJIFILM Medical, Bristol, Merck Serono |
Remuneration for lectures, written contributions, supervision of publications, etc., from the following companies:
|
Asahi Kasei Kuraray Medical, Ajinomoto, ASKA, Astellas, AstraZeneca, Abott, EN Otsuka, Eisai, MSD, Otsuka, Otsuka Pharmaceutical Factory, Olympus Medical Systems, KAKEN, Kyorin, Kyowa Hakko Kirin, GSK, Shionogi, JIMRO, Zeria, DAIICHI SANKYO, Tyco, Dainippon Sumitomo, Taiho, Takeda, Mitsubishi Tanabe, Chugai, TSUMURA, Terumo, TORAY, Torii, NIPPON KAYAKU, Nihon Schering, Novartis, FUJIFILM Medical, Bristol, Boston Scientific Japan, Merck Serono, Yakult, Janssen, UCB |
Provision of research funding from the following companies:
|
Asahi Kasei Kuraray Medical, Ajinomoto, Astellas, AstraZeneca, EN Otsuka, Eisai, MSD, Otsuka, Otsuka Pharmaceutical Factory, Olympus Medical Systems, KAKEN, Kyowa Hakko Kirin, Kyorin, KUREHA, GSK, Shionogi, JIMRO, J&J, Zeria, DAIICHI SANKYO, Tyco, Taisho Toyama, Dainippon Sumitomo, Taiho, Takeda, Mitsubishi Tanabe, Chugai, TSUMURA, Torii, Pfizer, FUJIFILM Medical, Bristol, MIYARISAN, Merck Serono, Yakult, UCB |
Company with potential conflicts of interest though family members:
|
Shionogi |
How to read the guidelines
I-1. Definition
CQ1: What is CD? [2]
-
CD is a chronic disease of unknown causes that mainly presents as granulomatous inflammatory lesions of the gastrointestinal tract. C1 (Japan VI, overseas VI; 8).
Comments
I-2. Epidemiology
CQ2: How common is CD, in what age group does it occur, and in Japan, are there any differences from other countries? [2‐7]
-
The number of CD patients in Japan is steadily increasing, with a current estimate of more than 30,000. CD is more prevalent among men than women, at an approximate ratio of 1.8: 1.0. B* (Japan V; 9).
-
CD occurs at comparatively young ages, more commonly from the late teens to the early 30s. B* (Japan V; 9)
-
The prevalence and incidence of CD in Europe and North America are higher than those in Japan, and female preponderance in those areas is noted. C1 (overseas V; 8).
Comments
I-3. Etiology
CQ3: What causes CD? Is it inherited? What are the risk factors? [8‐19]
-
The causes of CD have not been identified. C1 (Japan VI, overseas VI; 8).
-
A tendency for familial occurrence is noted. B (overseas IVa; 8).
-
Some causal relationships between diet and CD have been reported, though the evidence is not conclusive. B (Japan IVb, overseas IVb; 8).
-
Smoking is a risk factor for CD. B (overseas III; 8).
-
Nonsteroidal anti-inflammatory drugs (NSAIDs) and oral contraceptives are potential factors for the exacerbation of CD. C1 (overseas IVb; 7).
Comments
I-4. Pathophysiology, classification, and disease activity
CQ4: What kind of pathophysiological conditions are present in CD, and how are they recognized? [20]
-
To provide appropriate treatment, it is necessary to exactly recognize the disease extent, disease pattern, and degree of disease activity. B* (Japan VI, overseas: VI 9).
Comments
I-5. CD progression
CQ5: How does CD progress in the long term? Is there an increased risk of cancer? Is life expectancy shortened? [21‐29]
-
CD persists, with remissions and relapses, for a long period of time. C1 (Japan VI, overseas VI; 9).
-
During disease progression, the daily life of CD patients is often disturbed. C1 (Japan V, overseas V; 8).
-
The incidence of cancer among CD patients is slightly elevated. B (Japan V, overseas IVb; 8).
-
The life expectancy of CD patients is slightly shorter than that of healthy individuals. C1 (Japan V, overseas IVb; 7).
Comments
II-1. Clinical symptoms
CQ1: What are the clinical symptoms of CD? [30]
-
Abdominal pain and diarrhea are the most common symptoms. Symptoms due to perianal lesions and hematochezia are also commonly encountered. C1 (Japan VI, overseas V; 8).
-
Although systemic symptoms and signs such as weight loss, fever, general malaise and anorexia, and oral aphthous ulcerations are often observed, they are not highly specific for CD. C1 (Japan VI, overseas V; 8).
Comments
CQ2: What are the complications associated with CD? [30‐35]
-
Intestinal complications of CD include stenosis, fistulas (internal and external), abscess formation, massive hemorrhage, and colorectal cancer. B* (Japan V, overseas V; 9).
-
Extra-intestinal complications of CD include joint lesions (e.g., joint pain, acute peripheral arthritis, and reactive arthritis), skin lesions (e.g., erythema nodosum, Sweet’s disease, and pyoderma gangrenosum), eye lesions (e.g., iritis and episcleritis), and primary sclerosing cholangitis (PSC). C1 (Japan V, overseas V; 8).
-
Complications to which children are susceptible include growth retardation, osteoporosis, and angitis. C1 (Japan V, overseas V; 7).
Comments
CQ3: What kind of perianal lesions are caused by CD? [36‐38]
-
Perianal lesions include anal fissures, anal ulcers, skin tags, anal fistulas, perianal abscesses, anovaginal fistulas, cavitating ulcers, piles, and anal canal cancer. C1 (Japan V, overseas V; 8).
Comments
II-2. Medical interview and physical examination
CQ4: What kind of symptoms and physical findings make CD suspected? [39]
-
Chronic abdominal pain and/or diarrhea in young individuals suggest the possibility of CD, especially when accompanied by weight loss and fever. C1 (Japan VI, overseas VI; 8).
-
On physical examination, characteristic perianal lesions (preferably checked by colorectal surgeons familiar with CD), findings similar to appendicitis, bowel obstruction, and rectal bleeding indicate CD. C1 (Japan VI, overseas VI; 7).
-
Although the onset of CD is usually at young ages, it is not rare in the elderly. C1 (Japan VI, overseas VI; 7).
Comments
II-3. Diagnostic strategies
CQ5: If CD is suspected, how do physicians proceed to the diagnosis? What kind of investigations are required? [40, 41]
-
Obtain blood tests to check for inflammatory activity, malnutrition, and iron-deficiency anemia. C1 (Japan VI, overseas VI; 8).
-
Use imaging procedures to check for morphological findings characteristic of CD. C1 (Japan VI, overseas VI; 8).
-
Exclude infectious enterocolitis (including tuberculosis), if necessary, by stool culture and other tests. C1 (Japan VI, overseas VI; 8).
-
Apply tests to check for intestinal complications according to the symptoms. C1 (Japan VI, overseas VI; 8).
Comments
CQ6: What morphological examinations are necessary to make a diagnosis of CD? [40, 41]
-
Lower-gastrointestinal endoscopy, barium enema radiography, small-intestinal radiography, upper-gastrointestinal endoscopy, upper-gastrointestinal contrast radiography, and histopathological examination are necessary. B* (Japan VI, overseas VI; 9).
Comments
CQ7: What kind of laboratory markers are useful to evaluate the activity of CD? [42‐44]
-
Markers of inflammatory response (CRP and ESR) are considered to correlate with the disease activity. C1 (Japan VI, overseas VI; 8).
-
Nutritional indices (serum total protein and serum albumin) also reflect the disease activity in many cases. C1 (Japan VI, overseas VI; 7).
-
There is no single index with which to quantitate disease activity to enable an objective assessment; therefore, it is necessary to assess CD disease activity in a comprehensive manner. C1 (Japan VI, overseas VI; 9).
Comments
II-4. Endoscopy
CQ8: When is endoscopic examination necessary to make a diagnosis of CD? [39, 40, 43‐46]
-
When clinical symptoms and the laboratory test results suggest CD, promptly examine the patient using lower-gastrointestinal endoscopy (including an observation of the terminal ileum) and histological evaluation of biopsy specimens. C1 (Japan VI, overseas VI; 8).
-
Examine the patient using upper-gastrointestinal endoscopy when a definitive diagnosis has not been made with lower-gastrointestinal endoscopy or when the patient complains of symptoms in the upper gastrointestinal tract. C1 (Japan VI, overseas VI; 8).
Comments
CQ9: What endoscopic findings are characteristic of CD? [46, 47]
-
Lower-gastrointestinal endoscopic findings characteristic of CD include discrete or segmental lesions (so-called skip lesions), a cobblestone-like appearance, longitudinal ulcers, irregular-shaped ulcers, multiple aphthous ulcerations, abnormal narrowing and/or stenosis, and fistulas (internal and/or external fistulas). B* (Japan V, overseas VI; 9).
-
Upper-gastrointestinal endoscopic findings characteristic of CD include a bamboo joint-like appearance, a notch-shaped appearance, cobblestone-like appearance, multiple aphthous ulcerations, erosion, irregular-shaped ulcers, bead-like protrusions, nodular folds, granular mucous membrane, and stenosis. C1 (Japan V, overseas VI; 8).
Comments
CQ10: Is examination of the entire gastrointestinal tract necessary in the diagnosis of CD? [40, 41, 47]
-
Examinations of the lower gastrointestinal tract (using endoscopy or barium enema radiography) are almost indispensable for making a diagnosis of CD. B* (Japan VI, overseas VI; 9).
-
Even after a definitive diagnosis has been made, it is preferable to examine the patient using small-intestinal contrast radiography and upper-gastrointestinal endoscopy. C1 (Japan VI, overseas VI; 8).
Comments
II-5. Contrast radiography
CQ11: When is contrast radiography necessary to make a diagnosis of CD? [47‐49]
-
As CD may be complicated with intestinal stenosis, fistulas, abscess, and/or adhesions, the addition of barium enema radiography to colonoscopy would be advisable. C1 (Japan VI, overseas VI; 8).
-
Even if a diagnosis of CD is made by barium enema radiography, small-intestinal contrast radiography is valuable to determine the extent of the lesions and to establish treatment strategies. C1 (Japan VI, overseas VI; 8).
Comments
CQ12: Which findings of contrast radiography are characteristic of CD? [49‐52]
-
Longitudinal ulcers (asymmetric sclerotic appearance), cobblestone-like appearance, stenosis, aphthous ulcerations, irregular-shaped ulcers, fissures, and fistulas are typically found. B* (Japan V, overseas VI; 9).
Comments
II-6. Other imaging procedures
CQ13: How can imaging procedures such as CT and abdominal ultrasonography (US) contribute to making a diagnosis of CD? [53]
-
CT and US are useful for evaluating the extent and severity of gastrointestinal inflammation, and for the detection of abscess formation. C1 (Japan VI, overseas VI; 8).
Comments
II-7. Histopathological examination
CQ14: What pathological findings are characteristic of CD? [52, 54]
-
Findings for a definitive diagnosis of CD include: (1) noncaseating epithelioid cell granuloma, (2) transmural inflammation, (3) fissure, and (4) ulcers. C1 (Japan VI, overseas VI; 8).
Comments
II-8. Definitive diagnosis
CQ15: How can a definitive diagnosis be made? What diagnostic criteria are used? [39]
-
If CD is suspected based on medical interview, physical examination, and laboratory test results, gastrointestinal investigations should be conducted. C1 (Japan VI, overseas VI; 9).
-
The Japanese proposed diagnostic criteria for Crohn’s disease [39] (Table 5) consist mainly of morphological findings of the gastrointestinal tract. C1 (Japan VI; 8).Table 5Proposed diagnostic criteria for Crohn’s disease in Japan (as revised in February 2011) [39]Major findingsA. Longitudinal ulceraB. Cobblestone-like appearanceC. Noncaseating epithelioid cell granulomabMinor findingsa. Irregular-shaped and/or quasi-circular ulcers or aphthous ulcerations found extensively in the gastrointestinal tractcb. Characteristic perianal lesionsdc. Characteristic gastric and/or duodenal lesionseDefinite1. Major finding A or Bf2. Major finding C, with minor finding a or b3. All minor findings a, b, and cSuspected1. Major finding C, with minor finding c2. Major finding A or B, but cannot be differentiated from ischemic colitis or ulcerative colitis3. Major finding C onlyg4. One or two minor findings
Comments
CQ16: If a diagnosis of CD is not definitive, what should be done? [54, 55]
-
In indeterminate colitis where it is difficult to differentiate CD from UC, choose treatment strategies for the more suspected disease, observe progress with regular check-ups, and make a definitive diagnosis as soon as the features of one or the other disorder become dominant. C1 (Japan VI, overseas VI; 8).
-
If the diagnosis of CD is not definitive, as in patients with only aphthous ulcerations, observe progress with regular check-ups, and a definitive diagnosis of CD can be made when morphological examinations fulfill the criteria for the diagnosis. C1 (Japan VI, overseas VI; 8).
Comments
II-9. Determination of severity
CQ17: How are the severity and activity of the disease determined? [40, 56, 57]
-
The severity and activity are usually determined on the basis of clinical symptoms. C1 (Japan VI, overseas VI; 7).
-
The IOIBD and CDAI can be used to quantify the disease activity, but these indices are not easy to use in daily clinical practice. C1 (Japan VI, overseas VI; 8).
Comments
CDAI | Complication | Inflammation (CRP) | Treatment response | |
---|---|---|---|---|
Mild | 150–220 | None | Slight rise | |
Moderate | 220–450 | No manifestation of complications such as bowel obstruction | Clear rise | No response to treatment for mild CD |
Severe | >450 | Bowel obstruction, abscess, and other features | Great rise | Poor treatment response |
III-1. Outline of treatment
CQ1: If a patient has a diagnosis of CD, what will the treatments be, and how will this affect the patient’s lifestyle? [56‐60]
-
In the active stage, the treatments are directed to induce remission; once remission is induced, the treatments are given to maintain remission for a prolonged period. B* (Japan VI, overseas VI; 9).
-
Therapeutic modalities include medical treatments, such as drug therapies and nutritional therapies, and surgical treatments. They are selected as monotherapy or combination therapy. B* (Japan VI, overseas: VI 9).
-
The majority of patients can live a normal daily life, with regular school life or working hours. In patients with severe or fulminant symptoms, or frequent relapses, the patient needs to be hospitalized, or requires surgical treatment, and faces dietary and lifestyle restrictions. C1 (Japan VI; 8).
Comments
III-2. Consultation
CQ2: Should a CD patient be referred to a specialist for the treatment? [21]
-
On many occasions in the management of CD, consultation with a specialist is necessary. B* (Japan VI, overseas VI; 9).
-
Consultation is required for nutritional therapy, anti-tumor necrosis factor (TNF) therapy, failure to maintain remission, and surgical treatment. B* (Japan VI, overseas VI; 9).
Comments
III-3. Hospitalization
CQ3: Under what circumstances should a CD patient be hospitalized? [57, 61, 62]
-
Consider hospitalization when the patient does not improve on outpatient treatment. B* (Japan VI, overseas VI; 9).
Comments
III-4. Exercise and social activities
CQ4: Does a CD patient require rest and restriction of social activities? [31, 60, 63, 64]
-
Generally, patients do not require rest or restriction of activities. C1 (Japan VI, overseas VI; 8).
-
Patients in the active phase with severe abdominal symptoms, a finding of systemic inflammation, and exhaustion should avoid excessive exercise. C1 (Japan VI; 8).
-
In the active phase of the disease, patients face restrictions of social activities, such as school or work, due to treatment or hospitalization. B (Japan IVb; 8).
Comments
III-5. Diet
CQ5: Is dietary therapy necessary for the treatment of CD? [21]
-
There are no specific dietary therapies to cure or improve CD. C1 (Japan VI, overseas: VI; 9).
-
For patients in the active phase, considerinflammation in the gastrointestinal tract when selecting foods, . C1 (Japan VI, overseas VI; 8).
-
Do not allow the patient to take food orally in the presence of severe inflammation or obstruction. C1 (Japan VI, overseas VI; 8).
Comments
CQ6: What kind of general dietary recommendations should be made? [15, 60]
-
Basic recommendations during the active phase include having a low-fat, low-residue diet with low levels of stimulants, and food high in protein and calories, to improve the nutritional state while keeping the intestinal tract at rest. C1 (Japan VI, overseas VI; 7).
-
In the remission phase, no strict dietary restrictions are necessary, but a low-fat diet is preferred. C1 (Japan IVb; 7).
-
The response of the gastrointestinal tract to foods varies considerably from person to person. Accordingly, individual patients should avoid specific foods that make their symptoms worse. C1 (Japan VI, overseas VI; 8).
Comments
III-6. Smoking
CQ7: Should a CD patient refrain from smoking? [65‐71]
-
Upon diagnosis, the patient with CD should quit smoking. B (overseas III; 8).
Comments
III-7. Alcohol drinking
CQ8: Should a CD patient refrain from drinking alcohol? [60]
-
It is not necessary to recommend to every patient with CD that they refrain from drinking alcohol. However, it is preferable to avoid excessive drinking and to stop drinking when the disease is in the active phase. C1 (Japan VI, overseas VI; 7).
Comments
IV-1. Treatment options
CQ1: What are the treatment options for CD, and in what combinations? [56‐58]
-
Treatment strategies include drug therapies, nutritional therapies, surgical therapies, and other modalities. Select the most appropriate treatments according to the severity, extent of the lesion, and disease pattern. C1 (Japan VI, overseas VI; 9).
-
Initially, or in a relapse, apply drug therapies and nutritional therapies as monotherapy or in combination, with the aim being to induce remission. C1 (Japan VI, overseas VI; 8).
-
In patients with intestinal stenosis, fistulas, abscesses, and/or perianal lesions, or in cases that are resistant to medical treatment, consider surgical treatment. C1 (Japan VI, overseas VI; 8).
-
Once remission is induced, maintain remission using drug therapies (5-aminosalicylic acid [5-ASA] preparations, immunomodulators, anti-TNF agents), and/or nutritional therapies as monotherapy or in combination. C1 (Japan VI, overseas VI; 9).
Comments
IV-2. Steroids
CQ2: When are steroids indicated? What kinds of benefits and harms are expected? [21, 59, 72‐74]
-
Steroids possess potent anti-inflammatory effects. They are effective in inducing remission, but ineffective for maintaining remission. A (Japan V; overseas I; 8).
-
Steroids may cause adverse effects, particularly with long-term administration. Thus, steroids should be administered mainly to induce remission, and the dosage should be tapered until they are discontinued. C1 (Japan VI, overseas VI; 8).
-
Steroids are indicated for patients with moderate to severe disease activity, as well as for mildly active disease that is refractory to 5-ASA preparations. A (Japan VI, overseas II; 8).
Comments
IV-3. 5-ASA preparations
CQ3: When are 5-ASA preparations indicated? What kinds of benefits and harms are expected? [75‐77]
-
5-ASA preparations have clinical efficacy in active CD. A (overseas I; 8).
-
During the remission phase, 5-ASA preparations have a limited effect on maintaining remission, but harm is minimal. A (overseas I; 8).
Comments
IV-4. Immunomodulators
CQ4: When are immunomodulators indicated? What kinds of benefits and harms are expected? [78, 79]
-
Azathioprine (AZA) and 6-mercaptopurine (6-MP)* are effective in inducing remission in CD, but their adverse effects should be noted. A (overseas I; 8) *Not covered by Japanese public health insurance.
-
AZA is effective in maintaining remission in CD, and has a steroid-sparing effect. A (overseas I; 9).
Comments
IV-5. Anti-TNF agents
CQ5: When are anti-TNF agents indicated? What kinds of benefits are expected? [80‐85]
-
Anti-TNF agents are effective to induce remission. A (overseas I; 9).
-
In CD patients brought into remission by anti-TNF agents, these agents are also effective for fistula-closure and remission maintenance. A (overseas I; 8).
-
When infliximab has not been successful, adalimumab may be effective in inducing remission and attenuating symptoms. A (overseas I; 8).
Comments
CQ6: What harms are anticipated with the use of anti-TNF agents? [81, 86‐92]
-
Cases of serious infections and cases of opportunistic infections have been reported among patients who received infliximab or adalimumab. B (overseas IVa; 8).
-
Infliximab increases the chance of tuberculosis infection (including reactivation). B (overseas IVa; 8).
-
The occurrence of malignant tumors, including lymphoma, was reported among patients who received infliximab. B (overseas IVa; 8).
-
The incidence of cancer in general among patients who received adalimumab does not seem to be different from that in the general population. C1 (overseas V; 8).
Comments
IV-6. Antimicrobial drugs
CQ7: When are antimicrobial drugs indicated, and what kinds of benefits and harms are anticipated? [93‐97]
-
Antimicrobial drugs* are sometimes effective in attenuating the clinical symptoms of CD. A (overseas I; 8). *Antimicrobial drugs are not covered by the Japanese public health insurance system when used for the treatment of CD.
-
These drugs are more effective for colonic lesions than for small-intestinal lesions. A (overseas II; 8).
Comments
IV-7. Enteral nutriton
CQ8: When is enteral nutrition indicated, and what kinds of benefits and harms are expected? [98‐105]
-
The efficacy of enteral nutrition for inducing remission in active CD is equivalent or slightly inferior to that of corticosteroids. A (Japan III, overseas I; 8).
-
Elemental diet therapy is effective in maintaining remission in CD. A (Japan II; 8).
-
Although enteral nutrition is safe, maintenance of the patient’s acceptance is often difficult. C1 (Japan VI; 8).
Comments
CQ9: Are there differences in the therapeutic effect between oligomeric and polymeric nutrients? [98, 99, 106, 107]
-
There are no significant differences between oligomeric and polymeric nutrients in terms of their efficacy in remission induction for active CD. A (Japan III, overseas I; 7).
Comments
CQ10: When is it necessary to administer enteral nutrients through a nasogastric tube?
-
A nasogastric tube is necessary in cases where enteral nutrients should be given at a fixed rate, the oral intake of such nutrients is difficult, or such nutrients need to be given to patients at home during sleep at night. C1 (Japan VI, overseas VI; 8).
Comments
IV-8. Parenteral nutrition
CQ11: When is parenteral nutrition indicated, and what kinds of benefits and harms are expected? [58, 107‐110]
-
Total parenteral nutrition (TPN) is indicated for patients with active CD who have serious malnutrition, frequent diarrhea, and/or a critical disease state with extensive small-intestinal lesions, or in patients who have severe stenosis in the intestinal tract, fistulas, abscess formation, massive hemorrhage, and/or severe perianal lesions. The patient must be fasting when parenteral nutrition is administered. C1 (Japan VI, overseas VI; 8).
-
Total parenteral nutrition (TPN) is efficacious in inducing remission in active CD, and has a therapeutic effect equivalent to that of enteral nutrition. B (Japan III, overseas III; 8).
-
When carrying out TPN, watch for complications such as sepsis and hepatic disorders. C1 (overseas V; 8).
Comments
IV-9. Cytapheresis
CQ12: When is cytapheresis indicated, and what kinds of benefits and harms are expected? [111]
-
Cytapheresis is indicated in patients with active CD with colonic involvement in whom drug and/or nutritional therapies are ineffective or inapplicable; the addition of granulocyte-monocyte apheresis (GMA) may accelerate induction of remission. C1 (Japan V; 7).
Comments
IV-10. Surgical treatment
CQ13: What kind of benefits and harms are expected with surgical treatment? [112‐114]
-
Surgical treatment for the complications of CD is expected to attenuate the symptoms and improve the QOL. B (overseas IVa; 9).
-
Surgical treatment reduces the doses of therapeutic drugs and thus the possibility of adverse effects. C1 (Japan V, overseas IVa; 7).
-
Surgical treatment involves the risk of postoperative complications such as short-bowel syndrome and anastomotic leaks. C1 (Japan V, overseas V; 8).
Comments
IV-11. Endoscopic treatment
CQ14: When is endoscopic balloon dilation indicated, and what kinds of benefits and harms are expected? [115, 116]
-
Endoscopic balloon dilation is indicated for benign stenosis with bowel obstruction in the gastrointestinal tract without accompanying deep ulcers or fistulas. C1 (Japan VI, overseas VI; 7).
-
This therapy may alleviate bowel obstruction and may avoid a surgical operation. C1 (Japan V, overseas V; 8).
-
Care must be taken with regard to complications such as perforation or restenosis. C1 (Japan V, overseas V; 9).
Comments
V-1. Mild to moderate
CQ1: How is treatment initiated for mildly to moderately active CD? [56, 75, 98, 99, 102, 117‐124]
-
Administer salazosulfapyridine (SASP) in patients with mildly to moderately active CD with colonic lesions. A (overseas II; 8).
-
SASP is not effective for small-intestinal lesions. B (overseas III; 8).
-
The effect of 5-ASA preparations is limited, but they lack serious side effects and are easy to administer. In practice, they are often chosen as a first-line drug. A (overseas I; 8).
-
Daily administration of 1,000 mg ciprofloxacin* is expected to have an effect similar to that of 5-ASA preparations for colonic lesions in CD. B (overseas III; 7) *Not covered by Japanese public health insurance for treatment of CD.
-
The remission induction effect of enteral nutrition for active CD is equivalent or slightly inferior to that of corticosteroids. A (Japan III, overseas I; 8).
Comments
V-2. Moderate to severe
CQ2: How is treatment initiated for moderately to severely active CD? [56, 73, 111, 119, 125‐128]
-
Administer oral steroids (prednisolone, approximately 40 mg daily). B (overseas III; 8).
-
In cases where steroids are not effective, consider administering an anti-TNF agent. A (overseas II; 8).
-
The remission induction effect of enteral nutrition for active CD is equivalent or somewhat inferior to that of corticosteroids. A (Japan III, overseas I; 8).
-
In active CD with colonic lesions for which drug and/or nutrition therapies are ineffective or inapplicable, the addition of GMA may be helpful. C1 (Japan V; 7).
Comments
V-3. Severe to fulminant
CQ3: How is treatment initiated for severe to fulminant CD? [56, 129]
-
The patient is generally hospitalized; as necessary; consider complete fasting, infusion of fluid, and/or blood transfusion, and administer an antimicrobial drug if the patient shows signs of infection. C1 (Japan VI, overseas VI; 8).
-
Exclude infections, and intravenously administer steroids (prednisolone equivalent to 40–60 mg daily). C1 (Japan VI, overseas VI; 8).
-
In cases resistant to steroids, consider administering an anti-TNF agent. C1 (overseas V; 8).
-
In cases where the patient’s general condition is poor, or unresponsive to medical therapies, consult with surgeons at an early opportunity. C1 (Japan VI, overseas VI; 8).
Comments
V-4. Therapies according to disease extent
CQ4: Are different therapies used for lesions in the small intestine, the colon, and both? [117, 118]
-
Treatment options vary according to the disease extent. C1 (Japan VI, overseas VI; 8).
-
SASP is effective only for colonic lesions. A (overseas II; 8).
-
Antimicrobial drugs* are more effective for colonic lesions than for small-intestinal lesions. B (overseas III; 8). *Not covered by Japanese public health insurance for treatment of CD.
-
Enteral nutrition is more effective for small-intestinal lesions than for colonic lesions. A (Japan III, overseas I; 8).
Comments
CQ5: What is the treatment for CD lesions in the upper gastrointestinal tract? [56, 57]
-
In cases of CD with upper-gastrointestinal lesions, administer a proton pump inhibitor (PPI).* C1 (overseas VI; 7) *Not covered by Japanese public health insurance for treatment of CD.
-
Administer steroids and/or immunomodulators, such as AZA or 6-MP, as necessary. C1 (overseas VI; 7).
-
In cases refractory to steroids, consider administering anti-TNF agents. C1 (overseas: VI; 8).
-
In patients with upper-gastrointestinal lesions with bowel obstruction, consider endoscopic dilation or surgical treatment. C1 (overseas VI; 8).
Comments
V-5. Perianal lesions
CQ6: What is the treatment for the perianal lesions of CD? [36, 82, 130‐132]
-
Treat the intestinal lesions first, and wait to see if the perianal lesions are attenuated. C1 (Japan VI, overseas VI; 8).
-
Anti-TNF agents are effective as medical therapy for anal fistulas. A (overseas II; 8).
-
Antimicrobial drugs and immunomodulators are effective therapies for anal fistulas. A (overseas I; 8).
-
The Seton procedure is an effective surgical treatment for anal fistulas. In severe cases, consider a stoma. B (Japan V, overseas V; 9).
Comments
V-6. Refractory cases
CQ7: What is the treatment for cases refractory to various medical treatment? [57, 133]
-
Consider surgical treatment in cases refractory to medical treatment without attenuation of complications. B* (Japan VI, overseas VI; 9).
-
The indication for surgical treatment should be determined with mutual communications among the gastroenterologist, the surgeon, and the patient. B* (Japan VI; 9).
Comments
V-7. Fistulas
CQ8: What is the treatment for fistulas? [82, 132, 134]
-
Immunomodulators are effective for treating fistulas, but their onset of the action is delayed. A (overseas I; 8).
-
Anti-TNF agents are effective for treating fistulas. A (overseas II; 9).
-
Surgical treatment is indicated in patients with internal fistulas causing severe malabsorption. B (Japan VI, overseas VI; 8).
-
Consider surgical treatment for fistulas with abscess formation. B*(Japan VI, overseas IV:9).
Comments
V-8. Stenosis
CQ9: What is the treatment for an intestinal stenosis due to CD? [115, 135, 136]
-
Administer steroids in patients with severe inflammation. C1 (Japan VI, overseas VI; 7).
-
Consider endoscopic dilation in patients in whom there has been no improvement with drug therapies or decompression. C1 (Japan V, overseas V; 7).
-
Consider surgery in patients whose condition has not been improved with medical treatment. B* (Japan V, overseas V; 9).
Comments
V-9. Hemorrhage
CQ10: What is the treatment for hemorrhage from the CD lesions? [137‐140]
-
First apply conservative management such as supportive care and drug therapies. C1 (Japan V, overseas V; 9).
-
Infliximab was reported to be effective in arresting hemorrhage. C1 (Japan V, overseas V; 8).
-
If conservative management is not successful in arresting hemorrhage, surgery is indicated. B* (Japan V, overseas V; 9).
Comments
V-10. Abscesses
CQ11: What diagnosis and treatment are used for abscesses due to CD? [141‐144]
-
Imaging examinations such as CT, US, and MRI are used to diagnose abscesses. B (JapanV, overseas IVb; 9).
-
Where possible, perform image-guided (e.g., CT-guided) percutaneous drainage. B (Japan V, overseas IV; 8).
-
In patients with abscesses in the perianal region, perform incision and drainage. B* (Japan V, overseas V; 9).
-
In patients in whom abscesses recur after percutaneous drainage or in those with fistulas, surgical treatment is likely to be necessary. B* (Japan V, overseas V; 8).
Comments
V-11. Extra-intestinal complications
CQ12: What is the treatment for extra-intestinal complications of CD? [145‐147]
-
In patients with active intestinal lesions, treat the intestinal inflammation. C1 (Japan V, overseas V; 8).
-
In patientss with pyoderma gangrenosum or uveitis, administer steroids. C1 (Japan V, overseas V; 8).
-
In patients with extra-intestinal complications, the usefulness of infliximab was reported. A (overseas II; 8).
Comments
VI-1. General principles for preventing relapse
CQ1: Are there any lifestyle factors that require attention to prevent relapse? [18, 70, 148, 149]
-
If the patient smokes, advise them to refrain from smoking. B (overseas III; 9).
-
Advise the patient to avoid irregular lifestyle and eating habits, and to refrain from excessive alcohol drinking. C1 (overseas VI; 7).
-
Advise the patient to adopt a lifestyle without excessive mental stress, to have as little stress as possible. C1 (overseas IVb; 7).
-
Advise the patient that in using an analgesic or an antipyretic, wherever possible to avoid NSAIDs. C1 (overseas IVb; 7).
Comments
CQ2: Are there any distinctive features of CD that make the disease likely to relapse? [31, 150]
-
CD patients with fistulas, perforation, or perianal lesions, and those who have had resection of the intestinal tract, are more susceptible to relapses. C1 (Japan V, overseas V; 7).
-
Patients with CD who have required steroids for induction of remission are more susceptible to relapses. C1 (overseas IV; 7).
Comments
VI-2. Drug treatment
CQ3: Which drugs are effective for maintaining remission of CD? [76, 79, 128, 151‐153]
-
AZA is effective in maintaining remission. A (overseas I; 9).
-
In patients in whom remission was induced by anti-TNF agents, the scheduled administration of anti-TNF agents is effective in maintaining remission. A (overseas II; 8).
-
5-ASA preparations are effective in maintaining remission postoperatively. B (overseas II; 7).
Comments
CQ4: How long should the treatment for remission be continued? [128, 152, 154]
-
If effective, it is advisable to continue the administration of AZA or 6-MP* for 3–4 years. C1 (overseas VI; 8) *Not covered by Japanese public health insurance for treatment of CD.
-
Scheduled administration of infliximab is effective for at least 1 year. A (overseas II; 8).
Comments
VI-3. Nutritional therapy
CQ5: Is home enteral nutrition effective in maintaining remission? [103, 155, 156]
-
Replacing half of the daily caloric intake by enteral nutrients is effective in maintaining remission. A (Japan II, overseas II; 8).
Comments
CQ6: How long should nutritional therapy be continued? [103, 155, 156]
-
Replacing half of the daily caloric intake by enteral nutrients is effective in maintaining remission for at least one year. A (Japan II, overseas II; 8).
Comments
CQ7: When is home parenteral nutrition (HPN) necessary, and how is it performed? [157]
-
In patients with short-bowel syndrome for whom sufficient nutritional care by enteral feeding is not possible, supply nutrition by infusion through a central venous line. C1 (Japan VI, overseas VI; 8).
Comments
VII-1. Indication for surgery
CQ1: How often is surgical treatment required for CD? [158, 159]
-
In Japan, the cumulative rate of surgical intervention for CD at 5 and 10 years after the onset is 30.3 and 70.8 %, respectively. The rates vary greatly from area to area in Europe and North America. C1 (Japan V, overseas V; 7).
Comments
CQ2: What are the absolute indications and the relative indications for surgery? [141, 160, 161]
-
Surgery is absolutely indicated in patients with perforation, massive hemorrhage, development of cancer, bowel obstruction not alleviated by medical therapies, and abscesses. B* (Japan V, overseas V; 9).
-
Surgery is relatively indicated in patients with refractory stenosis or internal and external fistulas, and in those refractory to medical treatment, or with refractory extra-intestinal complications (e.g., growth retardation, pyoderma gangrenosum), and refractory perianal lesions. C1 (Japan V, overseas: V; 8).
Comments
VII-2. Refractory to medical treatment
CQ3: What is the main principle guiding surgery on the intestine? [162, 163]
-
As CD involves the entire intestinal tract and often recurs, the intestinal tract should be preserved as much as possible. A (overseas II; 9).
-
Only the small portion of the intestinal tract causing stenosis or fistulas should be resected. Strictureplasty should be performed in patients with short fibrotic stenosis in the small intestine or in those with a short length of small intestine remaining. C1 (Japan V, overseas V; 9).
Comments
VII-3. Stenosis
CQ4: What kind of surgery is used to treat stenosis? [164‐166]
-
Only the area of the lesion causing the stenosis should be resected. Strictureplasty should be performed for a short segment of fibrotic stenosis in the small intestine or in patients with a short length of small intestine remaining. B (Japan V, overseas IVb; 8).
Comments
VII-4. Perianal lesions
CQ5: What kind of surgery is used to treat perianal lesions? [38, 167, 168]
-
Perianal lesions in CD are classified as primary lesions (cavitating ulcerative lesions due to CD), secondary refractory lesions (secondary lesions originating from a primary lesion via infection and other causes), and incidental lesions (lesions not associated with CD). C1 (overseas VI; 7).
-
For incidental lesions, use ordinary treatments generally appropriate for such lesions. C1 (Japan VI, overseas VI; 7).
-
Among the secondary refractory lesions, a Seton technique is used for low intersphincteric fistulas and ischiorectal fistulas. Consider creating a stoma in cases not responsive to the Seton technique or in those with fibrotic stenosis. C1 (Japan VI, overseas VI; 8).
Comments
CQ6: Is it possible to close a stoma later? [169, 170]
-
In principle, a stoma that has been created because of rectal/anal lesions in CD is not closed because the lesions tend to recur frequently if it is closed. C1 (Japan V, overseas V; 7).
Comments
VII-5. Postoperative management
CQ7: What is the relapse rate after surgical treatment? [171‐173]
-
Relapse after intestinal resection is frequently discovered early by means of endoscopic exploration. The cumulative reoperation rates were 16–43 % at 5 years and 26–65 % at 10 years. C1 (Japan V, overseas V; 8).
Comments
CQ8: What are the risk factors for a relapse? [164, 172, 174‐176]
-
Gender and the presence of granuloma are not significant risk factors. In patients who have had operations on the colonic lesions of CD, reoperation is not frequent. C1 (overseas V; 7).
-
The length of the uninvolved area in the resection margins is not a significant risk factor. C1 (overseas V; 7).
-
No consensus has been reached on the disease duration before the initial operation, the presence or absence of histological inflammation at the resection margins, or the types of anastomosis (end-to-end, end-to-side, or functional end-to-end) as risk factors. C1 (Japan VI, overseas VI; 8).
-
In patients where fistulization is the surgical indication, the reoperation rate may be higher in comparison with that in patients with a non-fistulizing type. B (overseas IVb; 8).
-
It was reported that there was little difference in terms of recurrence rates between strictureplasty and intestinal resection. C1 (overseas IVb: 7).
Comments
CQ9: How can postoperative relapse be prevented? [105, 177‐179]
-
There are no established measures to prevent relapse. C1 (Japan VI, overseas VI; 7).
-
5-ASA, 6-MP*, and metronidazole* may be effective in preventing a postoperative relapse. B (overseas II; 7). *Not covered by Japanese public health insurance for treatment of CD.
-
The effect of postoperative nutritional therapies to prevent relapse is unclear. C1 (Japan V; 7).
Comments
VIII-1 Routine follow-up schedule
CQ1: How are CD patients followed, and what kind of examinations are required? [180, 181]
-
Advise patients to have regular examinations, and observe changes in the clinical symptoms (abdominal pain, diarrhea, fever, and others). C1 (Japan VI, overseas VI; 8).
-
CRP, ESR, complete blood counts, and serum albumin level correlate with the disease activity. C1 (Japan VI, overseas VI; 8).
-
If changes in disease activity are noted, employ imaging examinations to observe the lesions. C1 (Japan VI, overseas VI; 8).
Comments
VIII-2. Morphological examination
CQ2: When is endoscopy or contrast radiography necessary? [150]
-
When changes in disease activity or pathophysiological conditions are noted (clinical relapse, or complications such as bowel obstruction, abscesses, and fistulas), it is advisable to perform diagnostic imaging such as endoscopy and contrast radiography to assess the disease. C1 (Japan VI, overseas VI; 8).
Comments
VIII-3. Cancer surveillance
CQ3: Is the risk of cancer increased in CD, and can it be prevented? [25, 26, 182‐185]
-
Both colonic and ileocolonic CD have a higher risk of colorectal and/or anal cancer than that in the general population. B (Japan IVb, overseas IVa: 8).
-
The incidence of small-intestinal cancer in patients with CD is low, but the relative risk is high in such patients. C1 (overseas IVa; 7).
-
There is no evidence that the administration of immunomodulators increases the incidence of malignant tumors. C1 (overseas IVa; 7).
-
Preventive measures against the occurrence of cancer in patients with CD are not known, but control of the intestinal inflammation is considered to be important. C1 (Japan VI, overseas VI: 7).
-
There are no data to clearly show that 5-ASA reduces the risk of colorectal cancer in CD. C1 (overseas VI; 7).
Comments
CQ4: How is cancer surveillance conducted? [25, 186]
-
There is no effective cancer surveillance program at present. C1 (Japan VI, overseas VI; 8).
Comments
CQ5: Does CD increase the risk of extra-intestinal malignant tumors, and how is surveillance for such tumors conducted? [185, 187, 188]
-
A combination of infliximab and immunomodulators may increase the risk of malignant lymphoma. C1 (overseas V; 7).
-
There is no established program for the surveillance of malignant tumors in regions other than the intestinal tract. C1 (Japan VI, overseas VI; 8).
Comments
IX-1. Pregnancy
CQ1: Is CD exacerbated during pregnancy or in relation to the menstrual cycle? [189]
-
There is no evidence that CD is exacerbated by either pregnancy or the menstrual cycle. C1 (Japan VI, overseas V; 8).
Comments
CQ2: Do CD patients have different fertility rates from those of healthy individuals? [190‐193]
-
Many reports indicate that patients with CD have reduced fertility; on the other hand, some other reports show no significant differences from fertility rates in the general population. B (overseas IVb; 8).
Comments
CQ3: Is modification of the treatment necessary for pregnant patients with CD? [194‐202]
-
Devise treatment strategies according to the disease activity, considering the benefits and harms of the drugs. C1 (Japan VI, overseas VI; 8).
-
Dominant overseas opinions are to treat pregnant CD patients similarly to non-pregnant patients. C1 (overseas VI; 8).
-
In Japan, 5-ASA preparations, small to medium doses of steroids, and nutritional therapies are considered to be relatively safe in pregnant patients, but it is desirable to avoid immunomodulators. C1 (Japan VI; 7).
-
When using nutritional therapies in pregnant patients, avoid excessive administration of vitamin A. C1 (Japan VI, overseas VI; 8).
-
There is a possibility that the administration of AZA or 6-MP is associated with pre-term delivery, low birth weight, and fetal malformation. C1 (overseas IVa; 7).
-
Infliximab has been reported to be relatively safe, but the relevant data are not sufficient. B (overseas IVb; 8).
Comments
CQ4: What is the treatment for CD exacerbation during pregnancy? [198, 199, 201‐203]
-
Devise treatment strategies according to the disease condition, considering the benefits and harms of the drugs. C1 (Japan VI, overseas VI; 8).
-
First increase the dose of a 5-ASA preparation, and reinforce nutritional therapy. C1 (Japan VI; 8).
-
If the result of the above is not sufficient, use steroids, an immunomodulator, and/or an anti-TNF agent, considering their benefits and harms. C1 (Japan VI; 7).
Comments
IX-2. Lactation
CQ5. What is the treatment for CD during a period of lactation? [202, 204, 205]
-
Only a few drugs have been proven to be safe during breastfeeding, but nutritional therapy is considered safe. C1 (Japan VI, overseas VI; 8).
-
Devise treatment strategies according to the disease activity, considering the benefits and harms. C1 (Japan VI, overseas VI; 8).