Crohn’s disease
Description of condition Crohn’s disease is a chronic, inflammatory bowel disease that mainly affects the gastro-intestinal tract. It is characterised by thickened areas of the gastro-intestinal wall with inflammation extending through all layers, deep ulceration and fissuring of the mucosa, and the presence of granulomas; affected areas may occur in any part of the gastro-intestinal tract, interspersed with areas of relatively normal tissue. Crohn’s disease may present as recurrent attacks, with acute exacerbations combined with periods of remission or less active disease. Symptoms depend on the site of disease but may include abdominal pain, diarrhoea, fever, weight loss, and rectal bleeding.
Complications of Crohn’s disease include intestinal strictures, abscesses in the wall of the intestine or adjacent structures, fistulae, anaemia, malnutrition, colorectal and small bowel cancers, and growth failure and delayed puberty in children. Crohn’s disease may also be associated with extra-intestinal manifestation: the most common are arthritis and abnormalities of the joints, eyes, liver and skin. Crohn’s disease is also a cause of secondary osteoporosis and those at greatest risk should be monitored for osteopenia and assessed for the risk of fractures. Up to a third of patients with Crohn’s disease are diagnosed before the age of 21 years but there is a lack of evidence regarding treatment for children. Paediatric practice is often based on extrapolation from adult studies. Fistulating Crohn’s disease Fistulating Crohn’s disease is a complication that involves the formation of a fistula between the intestine and adjacent structures, such as perianal skin, bladder, and vagina. It occurs in about one quarter of patients, mostly when the disease involves the ileocolonic area. Aims of treatment Treatment is largely directed at the induction and maintenance of remission and the relief of symptoms. Active treatment of acute Crohn’s disease should be distinguished from preventing relapse. The aims of drug treatment are to reduce symptoms and maintain or improve quality of life, while minimising toxicity related to drugs over both the short and long term. Drug treatment should always be initiated by a paediatric gastroenterologist. In fistulating Crohn’s disease, surgery and medical treatment aim to close and maintain closure of the fistula. Non-drug treatment gIn addition to drug treatment, management options for Crohn’s disease include smoking cessation and attention to nutrition, which plays an important role in supportive care. Surgery may be considered in certain children with early disease limited to the distal ileum and in severe or chronic active disease.
Drug treatment Treatment of acute disease Monotherapy gA corticosteroid (either prednisolone or methylprednisolone or intravenous hydrocortisone ), is used to induce remission in children with a first presentation or a single inflammatory exacerbation of Crohn’s disease in a 12-month period. Enteral nutrition is an alternative to a corticosteroid when there is concern about growth or side effects. In children with distal ileal, ileocaecal or right-sided colonic disease, in whom a conventional corticosteroid is unsuitable or contra-indicated, budesonide [unlicensed] may be considered. Budesonide is less effective but may cause fewer side-effects than other corticosteroids, as systemic exposure is limited. Aminosalicylates (such as sulfasalazine and mesalazine ) are an alternative option in these children. They are less effective than a corticosteroid or budesonide [unlicensed], but may be preferred because they have fewer side-effects. Aminosalicylates and budesonide are not appropriate for severe presentations or exacerbations.h Add-on treatment gAdd on treatment is prescribed if there are two or more inflammatory exacerbations in a 12-month period, or the corticosteroid dose cannot be reduced. Azathioprine or mercaptopurine [unlicensed indications] can be added to a corticosteroid or budesonide to induce remission. In children who cannot tolerate azathioprine or mercaptopurine or in whom thiopurine methyltransferase (TPMT) activity is deficient, methotrexate can be added to a corticosteroid. Under specialist supervision, monoclonal antibody therapies, adalimumab and infliximab , are options for the treatment of severe, active Crohn’s disease, following inadequate response to conventional therapies or in those who are intolerant of or have contra-indications to conventional therapy.hSee also National funding/access decisions for adalimumab and infliximab. gAdalimumab and infliximab can be used as monotherapy or combined with an immunosuppressant, although there is uncertainty about the comparative effectiveness.hThere are concerns about the long-term safety of adalimumab and infliximab in children; malignancies, including hepatosplenic T- cell lymphoma, have been reported. Maintenance of remission gChildren, and their parents or carers, should be made aware of the risk of relapse with and without drug treatment, and symptoms that may suggest a relapse (most frequently unintended weight loss, abdominal pain, diarrhoea and general ill-health). For those who choose not to receive maintenance treatment during remission, a suitable follow up plan should be agreed upon and information provided on how to access healthcare if a relapse should occur. Azathioprine or mercaptopurine [unlicensed indications] as monotherapy can be used to maintain remission when previously used with a corticosteroid to induce remission. They may also be used in children who have not previously received these drugs (particularly those with adverse prognostic factors such as early age of onset, perianal disease, corticosteroid use at presentation, and severe presentations). Methotrexate [unlicensed] can be used to maintain remission only in children who required methotrexate to induce remission, or who are intolerant of or are not suitable for azathioprine or mercaptopurine for maintenance. Corticosteroids or budesonide should not be used.h Maintaining remission following surgery gAzathioprine or mercaptopurine can be considered to maintain remission after surgery in children with adverse prognostic factors such as more than one resection, or previously complicated or debilitating disease (for example, abscess, involvement of adjacent structures, fistulating or penetrating disease). Aminosalicylates can also be considered as an option, however budesonide or enteral nutrition should not be used.h Other treatments gLoperamide hydrochloride can be used to manage diarrhoea associated with Crohn’s disease in children who do not have colitis.hColestyramine is licensed for the relief of diarrhoea associated with Crohn’s disease. See also Acute diarrhoea . Fistulating Crohn’s disease Perianal fistulae are the most common occurrence in children with fistulating Crohn’s disease.gTreatment may not be necessary for simple, asymptomatic perianal fistulae. When fistulae are symptomatic, local drainage and surgery may be required in conjunction with medical therapy. Metronidazole or ciprofloxacin [unlicensed indications], alone or in combination, can improve symptoms of fistulating Crohn’s disease but complete healing occurs rarely. Metronidazole should be given for at least 6 weeks but no longer than 3 months because of concerns about peripheral neuropathy. Other antibacterials should be given if specifically indicated (e.g. in sepsis associated with fistulae and perianal disease) and for managing bacterial overgrowth in the small bowel. Either azathioprine or mercaptopurine [unlicensed indications] is used to control the inflammation in perianal and enterocutaneous fistulating Crohn’s disease and they are continued for maintenance. Infliximab is recommended for children with perianal and enterocutaneous active fistulating Crohn’s disease who have not responded to conventional therapy (including antibacterials, drainage and immunosuppressive treatments), or who are intolerant of or have contraindications to conventional therapy. Infliximab should be used after ensuring that all sepsis is actively draining. Abscess drainage, fistulotomy, and seton insertion may be appropriate, particularly before infliximab treatment. Azathioprine, mercaptopurine or infliximab should be continued as maintenance treatment for at least one year. For the management of non-perianal fistulating Crohn’s disease (including entero-gynaecological and enterovesical fistulae) surgery is the only recommended approach.
Description of condition Crohn’s disease is a chronic, inflammatory bowel disease that mainly affects the gastro-intestinal tract. It is characterised by thickened areas of the gastro-intestinal wall with inflammation extending through all layers, deep ulceration and fissuring of the mucosa, and the presence of granulomas; affected areas may occur in any part of the gastro-intestinal tract, interspersed with areas of relatively normal tissue. Crohn’s disease may present as recurrent attacks, with acute exacerbations combined with periods of remission or less active disease. Symptoms depend on the site of disease but may include abdominal pain, diarrhoea, fever, weight loss, and rectal bleeding.
Complications of Crohn’s disease include intestinal strictures, abscesses in the wall of the intestine or adjacent structures, fistulae, anaemia, malnutrition, colorectal and small bowel cancers, and growth failure and delayed puberty in children. Crohn’s disease may also be associated with extra-intestinal manifestation: the most common are arthritis and abnormalities of the joints, eyes, liver and skin. Crohn’s disease is also a cause of secondary osteoporosis and those at greatest risk should be monitored for osteopenia and assessed for the risk of fractures. Up to a third of patients with Crohn’s disease are diagnosed before the age of 21 years but there is a lack of evidence regarding treatment for children. Paediatric practice is often based on extrapolation from adult studies. Fistulating Crohn’s disease Fistulating Crohn’s disease is a complication that involves the formation of a fistula between the intestine and adjacent structures, such as perianal skin, bladder, and vagina. It occurs in about one quarter of patients, mostly when the disease involves the ileocolonic area. Aims of treatment Treatment is largely directed at the induction and maintenance of remission and the relief of symptoms. Active treatment of acute Crohn’s disease should be distinguished from preventing relapse. The aims of drug treatment are to reduce symptoms and maintain or improve quality of life, while minimising toxicity related to drugs over both the short and long term. Drug treatment should always be initiated by a paediatric gastroenterologist. In fistulating Crohn’s disease, surgery and medical treatment aim to close and maintain closure of the fistula. Non-drug treatment gIn addition to drug treatment, management options for Crohn’s disease include smoking cessation and attention to nutrition, which plays an important role in supportive care. Surgery may be considered in certain children with early disease limited to the distal ileum and in severe or chronic active disease.
Drug treatment Treatment of acute disease Monotherapy gA corticosteroid (either prednisolone or methylprednisolone or intravenous hydrocortisone ), is used to induce remission in children with a first presentation or a single inflammatory exacerbation of Crohn’s disease in a 12-month period. Enteral nutrition is an alternative to a corticosteroid when there is concern about growth or side effects. In children with distal ileal, ileocaecal or right-sided colonic disease, in whom a conventional corticosteroid is unsuitable or contra-indicated, budesonide [unlicensed] may be considered. Budesonide is less effective but may cause fewer side-effects than other corticosteroids, as systemic exposure is limited. Aminosalicylates (such as sulfasalazine and mesalazine ) are an alternative option in these children. They are less effective than a corticosteroid or budesonide [unlicensed], but may be preferred because they have fewer side-effects. Aminosalicylates and budesonide are not appropriate for severe presentations or exacerbations.h Add-on treatment gAdd on treatment is prescribed if there are two or more inflammatory exacerbations in a 12-month period, or the corticosteroid dose cannot be reduced. Azathioprine or mercaptopurine [unlicensed indications] can be added to a corticosteroid or budesonide to induce remission. In children who cannot tolerate azathioprine or mercaptopurine or in whom thiopurine methyltransferase (TPMT) activity is deficient, methotrexate can be added to a corticosteroid. Under specialist supervision, monoclonal antibody therapies, adalimumab and infliximab , are options for the treatment of severe, active Crohn’s disease, following inadequate response to conventional therapies or in those who are intolerant of or have contra-indications to conventional therapy.hSee also National funding/access decisions for adalimumab and infliximab. gAdalimumab and infliximab can be used as monotherapy or combined with an immunosuppressant, although there is uncertainty about the comparative effectiveness.hThere are concerns about the long-term safety of adalimumab and infliximab in children; malignancies, including hepatosplenic T- cell lymphoma, have been reported. Maintenance of remission gChildren, and their parents or carers, should be made aware of the risk of relapse with and without drug treatment, and symptoms that may suggest a relapse (most frequently unintended weight loss, abdominal pain, diarrhoea and general ill-health). For those who choose not to receive maintenance treatment during remission, a suitable follow up plan should be agreed upon and information provided on how to access healthcare if a relapse should occur. Azathioprine or mercaptopurine [unlicensed indications] as monotherapy can be used to maintain remission when previously used with a corticosteroid to induce remission. They may also be used in children who have not previously received these drugs (particularly those with adverse prognostic factors such as early age of onset, perianal disease, corticosteroid use at presentation, and severe presentations). Methotrexate [unlicensed] can be used to maintain remission only in children who required methotrexate to induce remission, or who are intolerant of or are not suitable for azathioprine or mercaptopurine for maintenance. Corticosteroids or budesonide should not be used.h Maintaining remission following surgery gAzathioprine or mercaptopurine can be considered to maintain remission after surgery in children with adverse prognostic factors such as more than one resection, or previously complicated or debilitating disease (for example, abscess, involvement of adjacent structures, fistulating or penetrating disease). Aminosalicylates can also be considered as an option, however budesonide or enteral nutrition should not be used.h Other treatments gLoperamide hydrochloride can be used to manage diarrhoea associated with Crohn’s disease in children who do not have colitis.hColestyramine is licensed for the relief of diarrhoea associated with Crohn’s disease. See also Acute diarrhoea . Fistulating Crohn’s disease Perianal fistulae are the most common occurrence in children with fistulating Crohn’s disease.gTreatment may not be necessary for simple, asymptomatic perianal fistulae. When fistulae are symptomatic, local drainage and surgery may be required in conjunction with medical therapy. Metronidazole or ciprofloxacin [unlicensed indications], alone or in combination, can improve symptoms of fistulating Crohn’s disease but complete healing occurs rarely. Metronidazole should be given for at least 6 weeks but no longer than 3 months because of concerns about peripheral neuropathy. Other antibacterials should be given if specifically indicated (e.g. in sepsis associated with fistulae and perianal disease) and for managing bacterial overgrowth in the small bowel. Either azathioprine or mercaptopurine [unlicensed indications] is used to control the inflammation in perianal and enterocutaneous fistulating Crohn’s disease and they are continued for maintenance. Infliximab is recommended for children with perianal and enterocutaneous active fistulating Crohn’s disease who have not responded to conventional therapy (including antibacterials, drainage and immunosuppressive treatments), or who are intolerant of or have contraindications to conventional therapy. Infliximab should be used after ensuring that all sepsis is actively draining. Abscess drainage, fistulotomy, and seton insertion may be appropriate, particularly before infliximab treatment. Azathioprine, mercaptopurine or infliximab should be continued as maintenance treatment for at least one year. For the management of non-perianal fistulating Crohn’s disease (including entero-gynaecological and enterovesical fistulae) surgery is the only recommended approach.