Edit concept Question Editor Create issue ticket

Pediatric Crohn's Disease

Crohn's Disease in Childhood

Crohn's disease belongs to the chronic inflammatory bowel diseases cluster, together with ulcerative colitis. It has a relapsing and remitting character and occurs in genetically susceptible individuals exposed to harmful environmental stimuli, resulting in abnormal activation of the immune system in the digestive tract. This disease is now considered one of the most important chronic diseases of the childhood.


Presentation

During history inquiry of a suspected Crohn's disease child, the physician should focus on personal complaints and growth curves, but should not forget about family history of intestinal diseases. The most frequent presenting symptom is represented by abdominal pain (possibly caused by pancreatitis), closely followed by weight loss and diarrhea. Traces of blood may be observed in the stool in almost half of cases, while 38% of children are febrile.

In general, the signs of the disease depend on the digestive tract segment involved. This condition may extend from the mouth to the anus. The terminal portion of the ileum is most frequently affected, followed by the ascending colon, stomach and duodenum. Children under 10 often experience the colonic form of the disease, while adolescents more commonly have terminal ileal and ileocecal involvement.

Upper gastrointestinal tract involvement manifests as nausea, vomiting and abdominal pain. When the small intestine is affected, children experience malabsorption, manifested as growth deceleration or failure, weight loss and diarrhea. Additionally, they complain about abdominal pain and anorexia, that potentates the failure to thrive process. Colonic Crohn's disease manifests and diarrhea with mucus, blood and puss, urgent defecation and abdominal cramps, while perianal Crohn's disease is suspected when physical examination reveals the presence of fistulae, abscesses or fissures in this area. These abnormalities cause pain during repose and during defecation and anal bleeding. In some patients, a palpable thickened loop of bowel located in the right lower quadrant of the abdomen may be palpated.

The severity and chronic character of the malabsorbtive process is evaluated using several parameters, such as growth velocity, skeletal bone age, body composition, height, weight, percentage weight for height and percentage height and weight for age.

Additional systemic findings on clinical examination are represented by tachycardia and paleness in anemic patients, pubertal delay and chronic intermittent fever. The disease is accompanied by a variety of extraintestinal manifestations. Dermatological signs of this condition include alopecia, pyoderma gangrenosum, erythema nodosum, acrodermatitis enteropathica, aphthous stomatitis and orofacial granulomatosis [1].

Ocular symptoms occur during the active periods of the disease and consist of pain or decreased visual acuity and signify the presence of episcleritis, iritis, uveitis or conjunctivitis. Increased intraocular pressure and cataracts may occur as complications of long-term corticoid therapy, making periodical ophthalmologic examination necessary.

Arthritis and arthralgia affect one quarter of pediatric Crohn's disease patients. Symptoms involve large joints of the inferior limbs, are transient and do not cause articular deformation. They may precede intestinal manifestations and may also involve sacroiliac articulations. The overall bone mass may be decreased, causing osteopenia or osteoporosis.

Cardio-pulmonary manifestations may be caused by myocarditis, pericarditis, fibrosing alveolitis or granulomatous lung disease or by thromboembolic disease (pulmonary embolism), as a result of a hypercoagulable state. Genitourinary manifestations may coexist, being caused by nephrolithiasis, hydronephrosis or glomerulonephritis, while concomitant hepatic disease may be represented by autoimmune or granulomatous hepatitis, primary sclerosing cholangitis, cholelithiasis or portal vein thrombosis.

Weight Loss
  • When the small intestine is affected, children experience malabsorption, manifested as growth deceleration or failure, weight loss and diarrhea.[symptoma.com]
  • Symptoms include fever, diarrhea, stomach cramps, vomiting, and weight loss. Regional enteritis increases the risk of colorectal cancer and small intestine cancer. It is a type of inflammatory bowel disease (ibd).[icd9data.com]
  • Symptoms include abdominal pain and diarrhea, sometimes bloody, and weight loss.[webmd.com]
  • It causes inflammation of your digestive tract, which can lead to abdominal pain, severe diarrhea, fatigue, weight loss and malnutrition. Inflammation caused by Crohn's disease can involve different areas of the digestive tract in different people.[mayoclinic.com]
Fever
  • Symptoms include fever, diarrhea, stomach cramps, vomiting, and weight loss. Regional enteritis increases the risk of colorectal cancer and small intestine cancer. It is a type of inflammatory bowel disease (ibd).[icd9data.com]
  • Rarely, people have fever. Abscesses deep in the rectum may be less painful but may cause fever and pain in the lower abdomen. A doctor's evaluation Rarely computed tomography A doctor can usually see an abscess if it is in the skin around the anus.[merckmanuals.com]
  • Fever. Fatigue. Loss of appetite and weight loss. Feeling that you need to pass stools, even though your bowels are already empty. It may involve straining, pain, and cramping. Watery diarrhea, which may be bloody.[nlm.nih.gov]
Fatigue
  • The main symptoms of Crohn's disease are: Crampy abdominal (belly area) pain Fever Fatigue Loss of appetite Pain with passing stool ( tenesmus ) Persistent, watery diarrhea Unintentional weight loss Other symptoms may include: Constipation Eye inflammation[web.archive.org]
  • It causes inflammation of your digestive tract, which can lead to abdominal pain, severe diarrhea, fatigue, weight loss and malnutrition. Inflammation caused by Crohn's disease can involve different areas of the digestive tract in different people.[mayoclinic.com]
  • Feeling fatigued? Enjoy regular exercise, a healthy diet, and enough sleep. And talk to your doctor. Taking antibiotics for Crohn's disease symptoms? Avoid alcohol, which can worsen some side effects.[web.archive.org]
  • Symptoms include pain, diarrhoea, fatigue and loss of weight. The row over the measles, mumps, rubella (MMR) vaccine focused on Crohn's disease as well as autism.[web.archive.org]
Anorexia
  • Additionally, they complain about abdominal pain and anorexia, that potentates the failure to thrive process.[symptoma.com]
  • In humans, cannabis has been used to treat a plethora of gastrointestinal problems, including anorexia, emesis, abdominal pain, diarrhea, and diabetic gastroparesis.[ncbi.nlm.nih.gov]
  • Systemic symptoms of malaise, anorexia, or fever are common. The history should include enquiry about possible extra-intestinal manifestations involving the mouth, skin, eyes and joints and episodes of perianal abscess or anal fissure.[patient.info]
Pallor
  • […] present in approximately 45% of patients Tanner staging may indicate pubertal delay, which may precede the onset of intestinal symptoms The most common cutaneous manifestations are erythema nodosum and pyoderma gangrenosum Skin examination may also reveal pallor[emedicine.medscape.com]
Abdominal Pain
  • BACKGROUND: Children with Crohn's disease (CD) may report abdominal pain despite clinical remission, suggesting that functional abdominal pain (FAP) may be playing a role.[ncbi.nlm.nih.gov]
  • Additionally, they complain about abdominal pain and anorexia, that potentates the failure to thrive process.[symptoma.com]
  • Symptoms include abdominal pain and diarrhea, sometimes bloody, and weight loss.[webmd.com]
  • It causes inflammation of your digestive tract, which can lead to abdominal pain, severe diarrhea, fatigue, weight loss and malnutrition. Inflammation caused by Crohn's disease can involve different areas of the digestive tract in different people.[mayoclinic.com]
Diarrhea
  • When the small intestine is affected, children experience malabsorption, manifested as growth deceleration or failure, weight loss and diarrhea.[symptoma.com]
  • Disease remission was defined by physician global assessment, normal laboratories findings, absence of 3 or more stools a day, nocturnal stooling, bloody diarrhea, concurrent steroid therapy, strictures, or disease flare within 6 months.[ncbi.nlm.nih.gov]
  • Day-to-day living is especially difficult if you suffer chronic symptoms like frequent diarrhea, gastrointestinal bleeding, anal tears, or bowel obstructions. Fortunately, treatments for Crohn's disease can make a big difference.[web.archive.org]
  • If you have chills, fever, pain, dizziness, or bloody diarrhea while away, call a doctor immediately.[webmd.com]
  • Symptoms include fever, diarrhea, stomach cramps, vomiting, and weight loss. Regional enteritis increases the risk of colorectal cancer and small intestine cancer. It is a type of inflammatory bowel disease (ibd).[icd9data.com]
Rectal Bleeding
  • bleeding and bloody stools Skin rash Swollen gums[web.archive.org]
  • Crohn's can cause diarrhea, fever, rectal bleeding, malnutrition, narrowing of the intestinal tract, obstructions, abscesses, cramping, and abdominal pain.[web.archive.org]
  • Rectal bleeding, fever, weight loss, arthritis, and anemia are indications of moderate to severe disease. Some patients develop fistulas, or abnormal passages connecting the bowel to other organs, such as the bladder or the vagina.[britannica.com]
  • The disease, most commonly diagnosed in people between the ages of 20 and 30, can cause abdominal pain, diarrhea, rectal bleeding, weight loss and arthritis. Chronic intestinal inflammation may necessitate the removal of sections of intestine.[web.archive.org]
  • Other symptoms may include: Constipation Sores or swelling in the eyes Draining of pus, mucus, or stools from around the rectum or anus (caused by something called a fistula ) Joint pain and swelling Mouth ulcers Rectal bleeding and bloody stools Swollen[nlm.nih.gov]
Nausea
  • The most common side effects of Cimzia are headache, upper respiratory infections, abdominal pain, injection site reactions and nausea.[web.archive.org]
  • Upper gastrointestinal tract involvement manifests as nausea, vomiting and abdominal pain. When the small intestine is affected, children experience malabsorption, manifested as growth deceleration or failure, weight loss and diarrhea.[symptoma.com]
  • The most frequently reported adverse events across the groups were headache (8%), rash (8%) and nausea (6%). Nausea led to discontinuation of treatment in three subjects, all in the 25 mg group.[doi.org]
  • A person may experience bloating and nausea for a short time after the test. For several days afterward, barium liquid in the GI tract causes stools to be white or light colored.[web.archive.org]
Vomiting
  • Symptoms include fever, diarrhea, stomach cramps, vomiting, and weight loss. Regional enteritis increases the risk of colorectal cancer and small intestine cancer. It is a type of inflammatory bowel disease (ibd).[icd9data.com]
  • Fluid and electrolytes (sodium, chloride, and potassium) are given by vein (intravenously) to replace water and salts lost from vomiting or diarrhea.[merckmanuals.com]
  • Upper gastrointestinal tract involvement manifests as nausea, vomiting and abdominal pain. When the small intestine is affected, children experience malabsorption, manifested as growth deceleration or failure, weight loss and diarrhea.[symptoma.com]
  • […] diarrhea with diet changes and drugs Have lost weight, or a child is not gaining weight Have rectal bleeding, drainage, or sores Have a fever that lasts for more than 2 or 3 days, or a fever higher than 100.4 F (38 C) without an illness Have nausea and vomiting[nlm.nih.gov]

Workup

Workup in pediatric Crohn's disease should be extensive and include common and relatively specific tests. The complete blood cell count may show the presence of anemia, that may be either hypochromic and microcytic, caused by chronic gastrointestinal blood loss or normocytic, similar to that found in other chronic diseases. This illness is accompanied by elevation of acute-phase reactants, such as the erythrocyte sedimentation rate and C-reactive protein. Calprotectin, often compared to an "erythrocyte sedimentation rate of the intestine" is increased in all inflammatory bowel disease cases [2]. Hypoalbuminemia, as well as diminished folic acid, calcium, magnesium, iron and vitamin B12 levels can also be encountered.

Since similar symptoms can be caused by parasitic infections, they must be ruled out by appropriate stool sample examination. Clinical distinction between pediatric Crohn's disease and pediatric ulcerative colitis is difficult, but it is aided by specific antibody examination: immunoglobulin A and G antibodies for Saccharomyces cerevisiae are more often increased in Crohn's disease, as opposed to perinuclear antineutrophil cytoplasmic antibodies, elevated in ulcerative colitis. However, the screening value of these parameters is considered low [3].

The definitive diagnosis is made by endoscopic and histological evaluation. Colonoscopy can now be performed even in infants, under appropriate sedation. The procedure must be accompanied by several terminal ileal biopsies, showing mucosal edema and inflammation that can have a transmural character, crypt abscesses with disturbed crypt architecture. The presence of granulomas further pleads for Crohn's disease. Granulomas can be disseminated throughout the entire digestive system, therefore an upper gastrointestinal tract endoscopy should also be performed. This method can evidentiate significant mucosal inflammation despite the absence of esophago-gastro-duodenal complaints. The mucosa is friable, ulcerated and edematous in a discontinuous manner, with affected areas alternating with normal patches. This aspect is characteristic to Crohn’s disease and allows macroscopical differentiation from ulcerative colitis.

These imaging methods, although reliable, can cause discomfort. For this reason, video capsule endoscopy is more and more frequently used in some centers [4]. However, prudence dictates that small bowel imaging should be performed first, to ensure that no strictures that may block its passage exist.

Small bowel inflammation can also be detected by magnetic resonance enterography, computed tomography enterography and single-contrast upper gastro-intestinal radiologic series. The first two methods can additionally describe extraenteric complications, such as fistulae and abscesses [5]. Magnetic resonance enterography, if available, may be best suited for children because it involves no radiation exposure. Additionally, it has high sensitivity and allows early diagnosis, making it the imaging method of choice for pediatricians worldwide [6]. Gallbladder and kidney stones are usually ruled out by abdominal ultrasonography.

Treatment

As any other chronic childhood condition, pediatric Crohn's disease brings, in addition to physical complaints, psycho-social repercussions. Therefore, one of the goals of therapy is to allow the patient to behave and function in a normal manner and to promote normal growth. Side effects of medication should be reduced to a minimum, and that is achieved by modulating therapy using a step-up approach. Mild disease responds to 5-aminosalicylic acid administration, combined with nutritional therapy and antibiotics, if needed. If no response is noted, the physician should add corticosteroid and immunomodulatory therapy (6-mercaptopurine or methotrexate). If the clinical condition still does not improve, biologic and surgical therapies are to be implemented.

Another treatment possibility is represented by the top-down approach, meaning that the biological therapy is introduced earlier in the therapeutic scheme. This method yielded better results in adults [7] and children [8], but further studies are needed. Complementary therapies with omega-3 fatty acids and probiotics have questionable results.

5-Acetylsalicylic acid is frequently used, but its efficacy is questionable [9]. The antibiotic classes proven to be beneficial in perianal, colonic and small disease are metronidazole and ciprofloxacin. Corticosteroids are especially useful in acute exacerbations, but systemic administration is not recommended for long-term use. However, when prolonged administration is imperative, the physician should prescribe enteric coated ileal-release preparations if available, as these have less systemic effects. 6-Mercaptopurine azathioprine and methotrexate have been proven to induce and maintain long-term disease remission [10]. They are especially useful in steroid dependent or resistant cases. However, certain cases prove unresponsive to all conventional therapy. They should receive biological therapy with monoclonal antibodies directed to tumor necrosis factor, either chimeric (Infliximab [11]) or humanized (Humira [12]). The latter is frequently indicated in patients that are allergic to Infliximab or in those who develop antibodies directed to the chimeric product. However, these products should be reserved for unresponsive cases, because some patients have developed a rare form of hepatosplenic T-cell lymphoma. Intractable pediatric Crohn's disease, as well as cases of perforation, stenosis, abscesses and severe hemorrhage benefit from surgery [13]. Unfortunately, recurrence after surgery is common and surgery is not curative. Laparoscopic techniques should be used, if possible, because of their decreased recovery time [14].

Prognosis

Pediatric Crohn's disease usually has a good prognosis, with extremely rare fatalities. However, life quality can be impaired by multiple surgeries, medication side effects or long hospitalizations. Pubertal delay can be encountered, as well as malnutrition and growth failure.

Etiology

The causes of pediatric Crohn's disease remain unknown. This condition is supposed to be a consequence of the interaction between genetic and environmental factors. 44.4% of monozygotic twins of affected individuals develop the condition [15]. The incriminated gene, NOD2/CARD15, is located on chromosome 16 and is responsible for the regulation of immune response to intestinal bacterial products [16]. Other gene mutations, like IL23R and ATG16L1 have also been demonstrated to be associated with Crohn's disease.

Epidemiology

Pediatric Crohn's disease is quite symmetrically found in Europe, Canada and North America: around 3.5 per 100,000 population, but it is rare in South America, Africa and Asia. Jewish children are more frequently affected. Girls and women suffer 1.1- 1.8 times more frequently from this condition. One study conducted in Wisconsin on pediatric population showed that this illness is twice more frequent than ulcerative colitis [17].

Sex distribution
Age distribution

Pathophysiology

Enteric bacteria or other antigens are thought to initiate an abnormal immune response in the gastrointestinal mucosa, leading to chronic inflammation. Helper lymphocytes type 1 response is poorly regulated, leading to the release of interleukin 12, tumor necrosis factor alpha, arachidonic acid metabolites, free radicals and platelet activating factor, with deleterious effects on the intestinal mucosa.

Prevention

Pediatric Crohn's disease cannot be prevented, but its complications sometimes can be, by timely and appropriate treatment. Frequent complications include fistulae, abscesses, strictures, adhesions and perforation. This latter entity presents as peritonitis and needs to be urgently addressed. Enterovesical and enterocutaneous fistulas are unpleasant complications, but not as severe as colonic malignancy. This is preceded by epithelial dysplasia, therefore routine colonoscopy and biopsy should be performed on a yearly basis.

Summary

Pediatric Crohn's disease is one of the most frequent chronic diseases of the childhood, causing symptoms that depend on the location and extent of the inflammatory mucosal lesions. Children fail to thrive due to the malabsorbtion this condition causes and complain about anorexia, weight loss, abdominal pain, urgency to defecate and diarrhea. Macroscopically, stools may contain mucus, blood and/ or puss. The perirectal area may be painful, as might be the defecation process, due to the presence of abscesses, fissures or fistulae in that region. The child may be febrile during the activity phase of the disease and may present with tachycardia caused by chronic anemia. Abdominal palpation may reveal the presence of a mass located in the right lower quadrant. Extraintestinal manifestation of pediatric Crohn's disease include erythema nodosum and pyoderma gangrenosum, episcleritis and anterior uveitis, arthritis and arthralgia of the large joints.

Laboratory tests highlight the presence of anemia, increased inflammatory markers levels, including fecal calprotectin. Micronutrients levels are low. The diagnosis is established via colonoscopy, accompanied by several colonic and ileal biopsies, showing the pathognomonic aspect of affected areas alternating with normal ones. The presence of crypts is also highly specific. As similar findings can be encountered in the superior digestive tract, an upper endoscopy or video capsule evaluation is recommendable. Additional imaging methods include single-contrast upper gastrointestinal radiologic series with small-bowel follow-through, magnetic resonance enterography and computed tomography enterography.

Treatment follows the step-up approach. It begins with 5-aminosalicylic acid preparations administration, combined with antibiotics and nutritional therapy. Non responders are switched to corticosteroid and immunomodulatory therapy with 6-mercaptopurine or methotrexate. The next step is represented by biological therapy with chimeric or humanized antibodies directed to tumor necrosis factor, while the last therapeutic resort is considered to be surgery, indicated for abscesses, fistulae, obstruction or stenosis, perforation, intractable disease or severe hemorrhage. Laparoscopic techniques are preferred.

Patient Information

Crohn's disease may be diagnosed during childhood, most frequently after the age of 10 years, but even babies can suffer from this condition. It can be found in several members of the same family and causes weight loss, anorexia, malabsorbtion, abdominal pain, diarrhea with blood and puss, skin conditions, ocular impairment and articular pain. Diagnosis is established using blood and stool samples, but also imaging techniques like colonoscopy, upper endoscopy, computer tomography and magnetic resonance imaging. The first two are frequently used because doctors can obtain tissue samples during the same session and have them analyzed. Treatment methods include several types of medicines, some that suppress the immune system, some that block the immune reactions and some that control bacterial growth. If these don not work, or if complications like intestinal perforation, obstruction, abscesses or fissures occur, surgery is indicated.

References

Article

  1. Aguirre A, Nugent CA. Images in Clinical Medicine: Oral Manifestation of Crohn's Disease. N Engl J Med. 2015;373(13):1250.
  2. Fagerberg UL, Loof L, Myrdal U, et al. Colorectal inflammation is well predicted by fecal calprotectin in children with gastrointestinal symptoms. J Pediatr Gastroenterol Nutr. 2005;40(4):450-5.
  3. Zholudev A, Zurakowski D, Young W, Leichtner A, Bousvaros A. Serologic testing with ANCA, ASCA, and anti-OmpC in children and young adults with Crohn's disease and ulcerative colitis: diagnostic value and correlation with disease phenotype. Am J Gastroenterol. 2004;99(11):2235-41.
  4. de Araujo G, Dubois J, Miron MC, Seidman EG. Wireless capsule endoscopy for obscure small-bowel disorders: final results of the first pediatric controlled trial. Clin Gastroenterol Hepatol. 2005;3(3):264-70.
  5. Lee SS, Kim AY, Yang SK, et al. Crohn disease of the small bowel: comparison of CT enterography, MR enterography, and small-bowel follow-through as diagnostic techniques. Radiology. 2009;251(3):751-61.
  6. Piekkala M, Kalajoki-Helmiö T, Martelius L, Pakarinen M, Rintala R, Kolho KL. Magnetic resonance enterography guiding treatment in children with Crohn's jejunoileitis. Acta Paediatr. 2012;101(6):631-6.
  7. D'Haens G, Baert F, van Assche G, et al. Early combined immunosuppression or conventional management in patients with newly diagnosed Crohn's disease: an open randomised trial. Lancet. 2008;371(9613):660-7.
  8. Kim MJ, Lee JS, Lee JH, Kim JY, Choe YH. Infliximab therapy in children with Crohn's disease: a one-year evaluation of efficacy comparing 'top-down' and 'step-up' strategies. Acta Paediatr. 2011;100(3):451-5.
  9. Akobeng AK, Gardener E. Oral 5-aminosalicylic acid for maintenance of medically-induced remission in Crohn's Disease. Cochrane Database Syst Rev. 2005. (1):CD003715.
  10. Uhlen S, Belbouab R, Narebski K, et al. Efficacy of methotrexate in pediatric Crohn's disease: a French multicenter study. Inflamm Bowel Dis. 2006;12(11):1053-7.
  11. Hyams J, Crandall W, Kugathasan S, et al. Induction and maintenance infliximab therapy for the treatment of moderate-to-severe Crohn's disease in children. Gastroenterology. 2007;132(3):863-73; quiz 1165-6.
  12. Hyams JS, Griffiths A, Markowitz J, et al. Safety and Efficacy of Adalimumab for Moderate to Severe Crohn's Disease in Children. Gastroenterology. 2012;143(2):365-74.
  13. Strong SA, Koltun WA, Hyman NH, Buie WD. Practice parameters for the surgical management of Crohn''s disease. Dis Colon Rectum. 2007;50(11):1735-46.
  14. von Allmen D, Markowitz JE, York A, Mamula P, Shepanski M, Baldassano R. Laparoscopic-assisted bowel resection offers advantages over open surgery for treatment of segmental Crohn's disease in children. J Pediatr Surg. 2003;38(6):963-5.
  15. Tysk C, Lindberg E, Jarnerot G, Floderus-Myrhed B. Ulcerative colitis and Crohn's disease in an unselected population of monozygotic and dizygotic twins. A study of heritability and the influence of smoking. Gut. 1988;29(7):990-6.
  16. Zeissig Y, Petersen BS, Milutinovic S, Bosse E, Mayr G, Peuker K, et al. XIAP variants in male Crohn's disease. Gut. 2015;64 (1):66-76.
  17. Kugathasan S, Judd RH, Hoffmann RG, et al. Epidemiologic and clinical characteristics of children with newly diagnosed inflammatory bowel disease in Wisconsin: a statewide population-based study. J Pediatr. 2003;143(4):525-31.

Ask Question

5000 Characters left Format the text using: # Heading, **bold**, _italic_. HTML code is not allowed.
By publishing this question you agree to the TOS and Privacy policy.
• Use a precise title for your question.
• Ask a specific question and provide age, sex, symptoms, type and duration of treatment.
• Respect your own and other people's privacy, never post full names or contact information.
• Inappropriate questions will be deleted.
• In urgent cases contact a physician, visit a hospital or call an emergency service!
Last updated: 2018-06-21 22:23