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.

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.

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].

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.

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.

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].

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.

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.

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.

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.

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