NORD gratefully acknowledges Andrew B. Grossman, MD, Division of Gastroenterology, Hepatology, and Nutrition, Children’s Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania, for assistance in the preparation of this report.
Pediatric Crohn’s disease is a rare, inflammatory bowel disease characterized by severe, chronic inflammation of the intestinal wall or any portion of the gastrointestinal tract. The gastrointestinal tract is a group of organs that are connected by tubes that run from the mouth to the anus. The organs that make up the gastrointestinal tract are the esophagus, stomach, small intestine, large intestine, and anus. The esophagus is the muscular tube that runs from the back of the throat to the stomach. The small intestine is a long, narrow, folded tube that extends from the stomach to the large intestine. It is the area where most of the digestion and absorption of nutrients occurs within the body. When the small intestine is damaged or lost (e.g., due to surgery), affected individuals may lose the ability to absorb sufficient amounts of water, vitamins and other nutrients from food. The large intestine, also known as the colon, is a long, narrow folded tube that connects the small intestine to the anus. The large intestine absorbs water and minerals and is where the formation and temporary storage of solid waste (feces) occurs. The anus is a small opening at the end of the intestines through which solid waste exits the body. The last segment of the large intestine that connects to the anus is called the rectum. Pediatric Crohn’s disease can affect any area of the gastrointestinal tract.
The two areas most often affected are the ileum and the large intestine. The ileum is the last section of the small intestine and connects to the large intestine. Common symptoms often include diarrhea (sometimes bloody), abdominal pain, fever, and weight loss. In pediatrics, poor linear growth and lack of adequate weight gain can often be the presenting concerns; in these instances, proper diagnosis is often delayed. Symptoms may come and go (relapsing and remitting). Crohn’s disease is more commonly diagnosed in adults, but approximately 25% are diagnosed as children and teenagers (pediatric population). Children and adolescents are less likely than adults to have disease that is limited to the small intestine. The exact cause of pediatric Crohn’s disease is not fully understood, but this is believed to develop because of multiple different factors occurring together including genetic, immunologic, and environmental triggers.
The signs and symptoms can vary from one person to another. Symptoms can appear suddenly, or they may build slowly over time. Symptoms may be triggered by trauma, illness, or stress. Sometimes, symptoms occur with no identifiable triggering event.
Common symptoms of pediatric Crohn’s disease are cramping, abdominal pain, and chronic episodes of watery diarrhea; blood may at times be seen in the diarrhea. Sometimes, affected individuals will have an urgent need to go to the bathroom and move their bowels. Some affected individuals may feel tired a lot and experience fever, nausea, or loss of appetite. Loss of appetite may cause some children to fail to gain weight and grow as would be expected for their age and gender. Affected individuals may exhibit malnutrition because of reduced intake of calories, and some may have difficulty absorbing nutrients in the intestines (malabsorption). As a result, they may be behind their peers in growth. Some children may experience a delay in reaching puberty.
Some affected children may develop bleeding within the gastrointestinal system. This bleeding can occur without being noticed. Sometimes, anemia may develop. Anemia is a condition in which there are low levels of circulating red blood cells. Red blood cells deliver oxygen throughout the body. Anemia is associated with fatigue, pale skin color (pallor), lightheadedness, and other symptoms.
About 30% of children and adolescents develop perianal disease, which affects the area around the anus. This can make it painful for children to go to the bathroom. Affected individuals may develop fissures or tears, abscesses, or a fistula in the perianal region. A fistula is a small, abnormal passageway that connects the skin to the inside of the anus. Fistulae can be associated with abscesses. Some individuals develop skin tags, which are raised areas or bumps off of the anus.
Some affected children develop narrowing of the affected area of the gastrointestinal tract. Over time scar tissue can form in the area of the narrowing, resulting in a stricture. This can hinder or block the passage of food through the large or small intestine and cause obstruction. A bowel obstruction can cause cramping, vomiting, and constipation.
Some affected individuals develop signs and symptoms outside of the gastrointestinal tract. These signs and symptoms may be called extraintestinal symptoms. About 40% of children or adolescents eventually develop lesions on or in the mouth, including lesions on the mucous membrane lining the inside of the mouth and on the gums (mucogingivitis), canker sores of the mouth (aphthous ulcers), or swelling.
In rare instances, children with pediatric Crohn’s disease develop lesions of the mouth and the perianal region, but with limited or mild intestinal disease.
There are additional symptoms that can occur in some children and adolescents with pediatric Crohn’s disease including an inflammatory skin condition called erythema nodosum, in which small, raised, reddish bumps develop on the skin. These bumps are often painful and occur most commonly on the shins. Some affected individuals may experience inflammation in the eyes, causing burning or itching eyes. Some affected individuals develop joint pain (arthralgia) or joint inflammation (arthritis).
The exact cause of pediatric Crohn’s disease is not fully understood. Most likely pediatric Crohn’s disease is a multifactorial disorder, which means that multiple factors must occur together for the disorder to develop. These factors can include genetic, immunologic, and environmental factors.
It is likely that pediatric Crohn’s disease develops, in part, because of malfunctioning of the body’s immune system. The immune system is the body’s natural defense system against foreign or invading organisms or substances. The immune system is a complex network of cells, tissues, organs, and proteins that work together to keep the body healthy. In pediatric Crohn’s disease, the immune system responds to a stimulus or ‘trigger’, often an infection, but the response is abnormal. The immune system does not shut off as it is supposed to and instead mistakenly targets the gastrointestinal system, and the large and small intestines in particular. This sustained and abnormal immune system activity causes chronic inflammation and irritation of the tissues of the gastrointestinal tract, resulting in the signs and symptoms of pediatric Crohn’s disease. Researchers are not sure why the immune system malfunctions, or why the gastrointestinal system is affected in pediatric Crohn’s disease.
Genetic factors play a role in some people with pediatric Crohn’s disease. If a family member has Crohn’s disease, then a related child has a greater chance of developing the disorder than people in the general population. Pediatric Crohn’s disease runs in the family in about of 15% of affected individuals. When someone has a genetic factor for a disorder, it is called a genetic predisposition. A genetic predisposition is when a person has a gene or genes associated with a particular disorder, but who will not develop the disorder unless other factors such as environmental or immunological ones are also present.
Several different genes have been shown to be altered (mutated) more often in children and adolescents with pediatric Crohn’s disease including the NOD2, ATG16L1, IL23R, and IRGM genes. Genes provide instructions for creating proteins that play a critical role in many functions of the body. When a gene is altered, the protein product may be faulty, inefficient, absent, or overproduced. The genes involved with pediatric Crohn’s disease are all involved with the function of the immune system.
Researchers have determined that there are more than 200 different genes that can be associated with Crohn’s disease and ulcerative colitis, another form of inflammatory bowel disease. Sometimes, the specific gene or genes involved in a disorder influence the specific signs or symptoms. This is called genotype-phenotype correlation. Researchers are still trying to determine whether there are any specific genotype-phenotype correlations in pediatric Crohn’s disease. If specific correlations can be made, this may help physicians predict disease course and help determine the most effective treatments.
Researchers have determined that genes that are involved with the interleukin 10 signaling pathway can cause a severe form of Crohn’s disease that is often present at or shortly after birth. An interleukin is a type of cytokine. Cytokines are specialized proteins secreted from certain immune system cells that either stimulate or inhibit the function of other immune system cells. Interleukin 10 is a cytokine that blocks inflammation in the body (anti-inflammatory). When genes in this pathway are altered (mutated), it may contribute to the unregulated inflammation seen in the gastrointestinal tract.
Environmental factors may include bacterial or viral infections. Environmental factors may directly damage the gastrointestinal tract or they may trigger the immune system to act, which then mistakenly damages the gastrointestinal tract. Other risk factors that may be associated with an increased risk of developing Crohn’s disease include frequent antibiotic use, consumption of a more Westernized diet, and history of smoking.
The intestines and stomach contain bacteria, which contribute to the gut microbiota. Researchers believe that some of these bacteria are beneficial to the body and help the immune system protect the body. When the gut microbiota is imbalanced – too little helpful bacteria, or too much unhelpful bacteria – it may increase the risk of an inflammatory bowel disease like pediatric Crohn’s disease. Why these shifts in the gut microbiota occur and how, specifically, they contribute to the development of pediatric Crohn’s disease is not fully understood.
Crohn’s disease is a common disorder, affecting as many as 780,000 people in the United States. The disorder is most common in individuals between 15-35, with approximately 25% diagnosed by age 20. There is another increase in frequency among individuals between 60-80 years of age. The frequency of pediatric Crohn’s disease is increasing; in particular, there has been a recent increase in the incidence of Crohn’s disease in children less than 6 years old; this is called very early onset (VEO) inflammatory bowel disease. Although more women are affected by Crohn’s disease than men, pediatric Crohn’s disease is more common in boys than girls. Pediatric Crohn’s disease is more common in Caucasians than in people of African descent. It is rare in people of Asian and Hispanic descent. Generally, Crohn’s disease is more severe among children and adolescents than in adults.
A diagnosis of pediatric Crohn’s disease is based upon identification of characteristic symptoms, a detailed patient and family history, a thorough clinical evaluation and a variety of specialized tests. Pediatric Crohn’s disease may be suspected in children or adolescents with chronic abdominal pain, diarrhea, weight loss, and anemia.
Clinical Testing and Workup
Children and adolescents suspected to have pediatric Crohn’s disease will receive a complete blood count. A complete blood count is a test that evaluates the cells in a person’s blood. In children and adolescents with pediatric Crohn’s disease there may be low levels of red blood cells (anemia), and high levels of white blood cells, which can indicate an inflammatory process in the body. A blood sample can also be used to determine an elevated erythrocyte sedimentation rate. This is a test that measures how long it takes red blood cells (erythrocytes) to settle in a test tube over a given period. Another test that can be run on a blood sample is a C-reactive protein test. C-reactive protein is released into the blood stream from the liver in response to inflammation within the body, including the inflammation that characterizes pediatric Crohn’s disease. Some affected individuals may have low levels of a protein called albumin in the blood (hypoalbuminemia). Although these tests can be positive in pediatric Crohn’s disease, there can be other causes for a positive result. These tests, in an of themselves, are not diagnostic. In addition, some affected children will be negative for these tests, meaning that if these tests are normal it doesn’t rule out the pediatric Crohn’s disease.
Doctors may request a stool sample. This sample can be tested to see if gastrointestinal symptoms are caused by a bacterial infection or parasite. A stool sample can also show that blood loss has occurred somewhere in the gastrointestinal tract. A stool sample can also be tested to detect the presence of a protein called calprotectin. Fecal calprotectin is a biomarker for inflammation of the mucosa, the mucous membranes that lines various organs and areas of the body. Biomarkers are measurable substances that can indicate the presence of disease; in this case, intestinal mucosal inflammation, which is indicative of an inflammatory bowel disease like pediatric Crohn’s disease.
Doctors may order traditional X-rays or specialized imaging techniques. Such imaging techniques may include computerized tomography (CT) scanning and magnetic resonance imaging (MRI). During CT scanning, a computer and X-rays are used to create a film showing cross-sectional images of certain tissue structures. An MRI uses a magnetic field and radio waves to produce cross-sectional images of particular organs and bodily tissues. These specialized x-ray tests can be used to assess and evaluate the health of the small and large intestines. A specific type of MRI called magnetic resonance enterography (MRE) can produced detailed images of the small intestine. An MRE can reveal inflammation, bleeding and other issues. A special type of CT scan called computed tomography enterography (taken with an oral contrast) can also produce detailed pictures of the small intestine. An oral contrast is a liquid that helps to produce detailed images of internal structures.
Some clinical centers use ultrasonography to produce images of the small intestine. Ultrasounds use high-frequency radio waves to create a picture or image (sonogram) of specific structures like internal organs. The radio waves bounce off of internal structures within the body and the echoes are recorded to create a sonogram.
Diagnostic testing for pediatric Crohn’s disease also includes direct visual examination of the large intestine by the insertion of a flexible, tube-like instrument (colonoscope) into the rectum (colonoscopy) or the removal and microscopic examination of small samples of rectal tissue (biopsy) to detect microscopic inflammation.
Doctors may order an upper endoscopy examination. This examination allows doctors to view the upper portion of the digestive tract including the esophagus, the stomach, and the first section of the small intestine called the duodenum. During this examination, doctors will run a thin, flexible tube (endoscope) down a person’s throat, then into the stomach, and eventually into the small intestine. This tube has a tiny camera attached to it that allows doctors to visually inspect these areas. This examination can reveal abnormal inflammation, irritation or swelling in these areas. An endoscopy examination also allows doctors to remove a small sample of tissue to be studied by for microscopic areas of inflammation. A colonoscopy involves using a colonoscope to view the rectum and the colon; this exam can show inflammation, irritation or swelling in these areas. Doctors can also take a biopsy sample during a colonoscopy.
The U.S. Food and Drug Administration (FDA) has approved the use of video capsule endoscopy in children over the age of 10. This test can help to diagnose Crohn’s disease as well as determine the severity of the disorder. Unlike an upper endoscopy, this exam allows physicians to exam the entire small intestine. A patient will swallow a small capsule that contains a tiny camera. As the capsule moves through the gastrointestinal tract, it snaps pictures at a rate of about two pictures per second. The pictures are wirelessly sent to a receiver. The capsule takes about eight hours to move through the gastrointestinal tract and permits doctors to view a length of the small intestine that cannot be reach by upper endoscopy or colonoscopy.
Treatment may require the coordinated efforts of a team of specialists. The treatment of pediatric Crohn’s disease is directed toward the specific symptoms that are apparent in each individual. Pediatricians, physicians who specialize in diagnosing and treating gastrointestinal disorders in children (pediatric gastroenterologists), pediatric surgeons, psychologists, dieticians, nutritionists and other healthcare professionals may need to systematically and comprehensively plan an affected child’s treatment.
Psychosocial support for the entire family is essential as well. Several of the organizations listed in the Resources section provide support and information on inflammatory bowel diseases like Crohn’s disease. There is no cure for Crohn’s disease, but with proper treatment and support the disease can be effectively managed and may go into remission for long periods of time. Affected children can lead fairly normal lives.
Specific therapeutic procedures and interventions may vary, depending upon numerous factors including the severity of the disease. Children will respond differently to therapy and the best therapy for one child may not be the same for another child. Decisions concerning the use of particular drug regimens and/or other treatments should be made by physicians and other members of the health care team in careful consultation with the patient (and parents) based upon the specifics of his or her case; a thorough discussion of the potential benefits and risks, including possible side effects and long-term effects; patient preference; and other appropriate factors.
The treatment options for pediatric Crohn’s disease can include medications, nutritional and diet therapy, and surgery. These therapies are often used in combination, with surgery being recommended when other therapies haven’t worked. The goals of therapy are to relieve symptoms and reduce inflammation, improve and optimize growth and well-being, and induce a remission to help prevent future complications.
Some children with mild or moderate disease will be given a drug called 5-aminosalicylic acid (5-ASA). In children with moderate or severe disease, doctors may try stronger anti-inflammatory drugs called corticosteroids, which are effective in treating active disease and achieving remission.
Some doctors may recommend antibiotics to treat bacteria found in the gut, which may be a contributing factor to the development of Crohn’s disease. Antibiotics are often used for mild or moderate disease as well as to treat infection associated with perianal disease, fistulae, and abscesses.
Drugs that modify the response of the immune system called immunomodulators may be used to induce or prolong remissions. Immunomodulator drugs most commonly utilized in the treatment of Crohn’s disease include 6-mercaptopurine and azathioprine, as well as methotrexate.
Drugs known as biologics can also be used to treat pediatric Crohn’s disease. Biologics are usually complex molecules that contain living organisms, or are produced from living organisms. Biologic medications for pediatric Crohn’s disease include the following:
In 2006, the FDA approved infliximab (Remicade) for the treatment of moderate to severe active Crohn’s disease in children aged 61-17 in whom other treatments have not been effective. Infliximab can reduce signs and symptoms and help to achieve and maintain remission.
In 2014, the FDA approved adalimumab (Humira) for the treatment of moderate to severe Crohn’s disease in children 6 years and older in whom certain other treatments haven’t been effective. Adalimumab reduces the signs and symptoms of pediatric Crohn’s disease and helps to achieve and maintain a remission.
Two medications, called vedolizumab (Entyvio) and ustekinumab (Stelara), have been approved by the FDA for the treatment of adult Crohn’s disease. These medications are sometimes used off-label in the treatment of pediatric Crohn’s disease.
Diet and Nutrition
Diet modifications and nutrition are important elements of treating pediatric Crohn’s disease. Although no specific diet has been proven to be most effective, there are foods that doctors may recommend avoiding because they are difficult to digest and could result in an obstruction in a narrowed segment of bowel. These foods include popcorn, uncooked vegetables, and nuts. Additionally, some food, such as milk, certain spices or spicy foods, may worsen symptoms for particular individuals.
The inflammation of the gastrointestinal tract that characterizes pediatric Crohn’s disease may make it difficult for the body to absorb nutrients. Affected children may then be unable to gain weight or grow properly. Sometimes, exclusive enteral nutrition (EEN) may be recommended. This involves consuming all calories from a special formula instead of regular diet. Often, this requires introducing the formula directly to the stomach through a nasogastric tube. A nasogastric tube is a thin tube that is inserted into the nostrils and runs down the throat to the stomach. The amount of time children will need exclusive enteral nutrition varies depending upon their specific symptoms and disease severity. While this can be helpful for improving nutritional status, EEN can also lead to remission of active disease.
Surgery may be necessary in children in whom previous medical therapies such as medications and diet and nutrition have failed. Surgery usually involves removing the diseased tissue, but the disease often recurs in nearby tissue; as many as 50% of children who undergo surgery require a second surgery at some point during their lives. In some children, severe disease that is resistant to therapy may require a larger portion of intestines to be removed. This can result in short bowel syndrome. Short bowel syndrome is a complex disease that occurs due to the physical loss or the loss of function of a portion of the small and/or large intestine. NORD has a separate report on short bowel syndrome.
Surgery may also be indicated for severe narrowing or obstruction of the intestines, bleeding that can’t be stopped by other means (intractable hemorrhaging), intestinal fistulae, and perforation, which is when a hole forms in the intestinal wall. Surgery may also be used to drain an abscess.
Information on current clinical trials is posted on the Internet at https://clinicaltrials.gov/. All studies receiving U.S. Government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Toll-free: (800) 411-1222
TTY: (866) 411-1010
Email: [email protected]
Some current clinical trials also are posted on the following page on the NORD website:
For information about clinical trials sponsored by private sources, contact:
For information about clinical trials conducted in Europe, contact:
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