Pediatric Crohn Disease Clinical Presentation

Patients with suspected Crohn disease should initially be evaluated by their primary care team. Symptoms should be elicited in detail. A medical history, a detailed review of systems, and a family history should be obtained, and growth parameters should be documented.

In a series of 386 pediatric patients with Crohn disease from the Hospital for Sick Children in Toronto, the distribution of presenting symptoms was as follows: abdominal pain in 86%, weight loss in 80%, diarrhea in 78%, blood in the stool in 49%, perianal lesions in 44%, and fever in 38%. ^[13]

The clinical presentation is primarily determined by the location and extent of the patient’s disease. The terminal ileum is involved in 50-70% of children. More than half of these patients also have inflammation in various segments of the colon, usually the ascending colon. Overall, children seem to be more likely than adults to have colonic involvement; approximately 10-20% have isolated colonic disease. Gastric inflammation, duodenal inflammation, or both may be observed in as many as 30-40% of children with Crohn disease.

Upper gastrointestinal Crohn disease

Patients with upper gastrointestinal (GI) Crohn disease condition may experience nausea, vomiting, and abdominal pain as dominating presenting symptoms.

Crohn disease of small intestine

Children with Crohn disease of the small intestine usually present with evidence of malabsorption, including diarrhea, abdominal pain, growth deceleration, weight loss, and anorexia. Initially, these symptoms may be quite subtle. The onset of growth failure is usually insidious, and any child or adolescent with persistent alterations in growth should undergo appropriate diagnostic evaluation for Crohn disease. Growth failure may precede GI symptoms by years.

Colonic Crohn disease

Colonic Crohn disease may be clinically indistinguishable from ulcerative colitis (UC), with symptoms of bloody mucopurulent diarrhea, cramping abdominal pain, and urgency to defecate (see the Table below).

Table. Characteristics and Presentations Differentiating Crohn Disease From Ulcerative Colitis (Open Table in a new window)

Perianal Crohn disease

Perianal involvement in Crohn disease includes simple skin tags, fissures, abscesses, and fistulae. Painful defecation, bright red rectal bleeding, and perirectal pain, erythema, or discharge may signal perianal disease and may occur without symptomatic involvement in any other area of the GI tract. The perineum should be inspected in all patients who present with signs and symptoms of Crohn disease because abnormalities detectable in this region substantially increase the clinical suspicion of inflammatory bowel disease (IBD).

Findings on physical examination depend on the duration and extent of the disease and on the extraintestinal manifestations.

Careful assessment of growth and development is an important part of evaluating the pediatric patient. Growth abnormalities may be detected by evaluating height and weight, percentage height and weight for the patient’s age and percentage weight for the patient’s height, growth velocity, body composition on anthropometry, and skeletal bone age. The most sensitive indicator of growth abnormalities is a decrease in growth velocity, which may be observed before the major percentile lines on standard growth curves are crossed.

Gupta et al identified risk factors for impaired statural growth in children with Crohn disease, which differ by sex. ^[14] Joint pain at symptom onset and the use of probiotics or azathioprine/6-mercaptopurine were associated with growth impairment among the girls in their study; whereas an initial classification of IBD as Crohn disease and anorexia or mouth sores at symptom onset were associated with reduced statural growth in boys. The researchers noted that growth impairment is generally more common in males with Crohn disease than in females.

Vital signs are usually normal, although tachycardia may be present with anemic patients. Chronic intermittent fever is a common presenting sign. Body weight and height may reveal weight loss and growth delay.

Abdominal findings may vary from normal to those of an acute abdomen. Diffuse abdominal tenderness is often present. Fullness or a discrete mass may be appreciated, typically in the right lower quadrant of the abdomen, which may represent a palpable thickened loop of bowel. Perianal disease (eg, skin tags, abscesses, fistulae, fissures) is present in approximately 45% of patients. Pubertal delay may precede the onset of intestinal symptoms, and accurate Tanner staging should be a part of routine physical examination.

The most common cutaneous manifestations of Crohn disease are erythema nodosum and pyoderma gangrenosum. Skin examination may also reveal pallor in patients with anemia or jaundice in those with concomitant liver disease. Eye examination may reveal episcleritis. For the diagnosis of uveitis, a slit lamp examination by an experienced physician is necessary.

The most common extraintestinal manifestations of Crohn disease are arthritis and arthralgia. The large joints (eg, hips, knees, ankles) are typically involved.

The major intestinal complications of Crohn disease are due to the transmural nature of the disease. This leads to the formation of abscesses, fistulae, sinus tracts (incomplete fistulae ending in a “cul-de-sac”), strictures, and adhesions, which may also contribute to obstruction.

Frank perforation is one of the most serious complications of Crohn disease. Perforation typically occurs into other segments of bowel, leading to fistulae, or into areas such as the retroperitoneum, resulting in abscess formation. The presenting features of frank perforation are those of classic peritonitis, though these features may be masked by high-dose corticosteroid therapy.

Fistula and abscess formation is common in Crohn disease and is due to transmural bowel perforation. Perianal and perirectal fistulization are most common. Proper evaluation of perianal disease requires a combination of 2 of the following:

• Pelvic magnetic resonance imaging (MRI)

• Examination under anesthesia

• Endoscopic ultrasonography

Other complications of fistulizing disease include enterovesical and enterocutaneous fistulas.

A study by Herman et al aimed to assess phenotypic features at diagnosis and long-term disease-specific outcomes in 296 children perianal Crohn's disease reported that fistulizing and nonfistulizing perianal disease was associated with worse outcomes. The study also reported that the presence of nonfistulizing disease at diagnosis was a significant risk factor for the development of fistulizing perianal disease (HR 3.4, P = 0.002) and that females were more associated with perianal involvement (P = 0.01). ^[15]

Colonic malignancy is a clinically significant complication of Crohn disease in patients with pancolitis beginning in childhood. Although the risk of malignancy in Crohn disease is not as high as that in UC, the risk of adenocarcinoma of the colon in Crohn colitis is 4-20 times that of the general population. Small intestinal carcinoma is 50-100 times more likely to develop in patients with small intestinal Crohn disease but is still rare.

The risk for children with an onset of disease in the first decade is unknown, but children who develop colitis when younger than 10 years should undergo colonoscopic screening during adolescence.

Epithelial dysplasia generally precedes carcinoma; therefore, yearly surveillance colonoscopy is recommended for patients with this condition, who are at high risk.

Extraintestinal manifestations

Approximately 25-35% of patients with Crohn disease have at least 1 extraintestinal manifestation, which may be diagnosed before, when, or after Crohn disease is diagnosed. These manifestations may carry prognostic importance.

Dermatologic manifestations of Crohn disease include the following:

• Erythema nodosum

• Pyoderma gangrenosum

• Orofacial granulomatosis ^[16]

• Angular and aphthous stomatitis

• Acrodermatitis enteropathica

• Alopecia

• Metastatic Crohn disease

• Crohn disease of the vulva and penis

Erythema nodosum is the most common skin manifestation of Crohn disease. It is more common in Crohn disease than in UC and usually follows the course of the disease. Erythema nodosum affects 3% of pediatric patients with Crohn disease (a lower rate than that in adults). Approximately 75% of patients with erythema nodosum ultimately develop arthritis. The lesions of erythema nodosum are raised, red, tender nodules that appear primarily on the anterior surfaces of the lower leg.

Pyoderma gangrenosum may also develop in Crohn disease, though it is uncommon in this setting. Pyoderma gangrenosum is often an indolent chronic ulcer, which may occur even when the disease is in remission. Therefore, medical therapy for the underlying bowel disease is not always successful.

Aphthous ulceration in the mouth is the most common oral manifestation of Crohn disease. This ulceration is commonly associated with skin and joint lesions. Oral lesions appear to parallel intestinal disease in most cases, but they may also occur before any GI symptoms occur.

Ophthalmologic manifestations of Crohn disease include the following:

• Episcleritis

• Uveitis, iritis

• Conjunctivitis

Ophthalmologic manifestations most frequently occur when the disease is active. The rate is 4% in the adult population but is lower in children and adolescents. Episcleritis and anterior uveitis are the most common ocular findings. The uveitis is usually symptomatic, causing pain or decreased visual acuity. Increased intraocular pressure and cataracts may be observed in children who receive corticosteroid therapy. All patients with Crohn disease require ophthalmologic examination at regular intervals.

Musculoskeletal manifestations of Crohn disease include the following:

• Arthralgia

• Arthritis

• Ankylosing spondylitis

• Sacroiliitis

Arthritis is the most common extraintestinal manifestation in children and adolescents (7-25% of pediatric patients). The arthritis is usually transient, nondeforming, asymmetric in distribution, and involves the large joints of the lower extremities. In adults, the arthritis occurs when the disease is active, but in children, the arthritis may occur years before any GI symptoms develop.

Bone metabolic disorders seen in Crohn disease include the following:

• Osteopenia

• Osteoporosis

Hematologic manifestations of Crohn disease include the following:

• Iron deficiency anemia

• Vitamin B-12 deficiency anemia

• Folate deficiency anemia

• Anemia of chronic disease

• Autoimmune hemolytic anemia

• Thrombocytosis

• Anemia due to GI bleeding

• Thrombosis

Hepatobiliary disease is one of the most common extraintestinal manifestations of Crohn disease and its therapies. Hepatobiliary manifestations include the following:

• Primary sclerosing cholangitis

• Autoimmune hepatitis

• Granulomatous hepatitis

• Cholelithiasis

• Portal vein thrombosis

Abnormal serum aminotransferases are common during the course of Crohn disease in children. Most aminotransferase elevations are transient and appear to relate to medications or disease activity. Persistent aminotransferase elevations (>6 months) should be investigated because the likelihood of serious liver disease is increased.

Both intrahepatic and extrahepatic manifestations of liver disease occur in children with Crohn disease. Intrahepatic manifestations include chronic active hepatitis, granulomatous hepatitis, amyloidosis, fatty liver, and pericholangitis. Extrahepatic manifestations include cholelithiasis and obstruction. Chronic active hepatitis and sclerosing cholangitis develop in fewer than 1% of children with Crohn disease.

Genitourinary manifestations of Crohn disease include the following:

• Nephrolithiasis

• Hydronephrosis

• Enterovesical fistulae

• Obstructive uropathy

• Glomerulonephritis

• Amyloidosis

Nephrolithiasis occurs in fewer than 5% of children with Crohn disease. It is usually the result of fat malabsorption that occurs with small bowel Crohn disease. Dietary calcium binds to malabsorbed fatty acids in the colonic lumen; therefore, free oxalate is absorbed. The absorption of free oxalate results in hyperoxaluria and oxalate stones. In patients with an ileostomy, increased fluid and electrolyte losses may lead to concentrated acidic urine and the formation of uric acid stones.

External compression of the ureter by an inflammatory mass or abscess may lead to hydronephrosis. Enterovesical fistulae may present with recurrent urinary tract infections or pneumaturia.

In the pancreas, Crohn disease may be manifested as pancreatitis.

Pulmonary manifestations of Crohn disease include the following:

• Granulomatous lung disease

• Fibrosing alveolitis

• Pulmonary vasculitis

Cardiovascular manifestations include the following:

• Pericarditis

• Myocarditis

• Vasculitis

Growth failure and delayed sexual development are common in adolescents and children with Crohn disease. Studies of the growth of these children have found that impairment of linear growth is common before diagnosis and in subsequent years. Decreased height velocity before the onset of intestinal symptoms can be observed in as many as 46% of patients with Tanner stage 1 or 2. Height at maturity is often compromised. The etiology of growth failure is multifactorial, with nutritional, hormonal, and disease-related factors all contributing.

Thromboembolic disease is considered the result of a hypercoagulable state that parallels disease activity and is manifested by thrombocytosis, elevated plasma fibrinogen, factor V, factor VIII, and decreased plasma antithrombin III. This may lead to deep vein thrombosis, pulmonary emboli, and neurovascular disease.