Diagnosis

The list of conditions that should be considered in the differential diagnosis for Crohn's disease is extensive, and is related to the various clinical presentations of Crohn's disease (Table 23.6). A high index of clinical suspicion is crucial if the clinician is to make a diagnosis in the early phases of the illness. Delay in growth is often a clue that the presenting symptoms are not caused by an acute illness.

Clinical suspicion for Crohn's disease

It is important to rule out Crohn's disease in any child with recurrent abdominal pain, chronic diarrhea, weight loss, blood in stools, growth delay, pubertal delay, unexplained anemia and perianal disease. Growth failure can be an important initial clue in suspecting Crohn's disease, since approximately half the children with Crohn's disease have a delay in height velocity prior to obvious intestinal manifestation.118 For patients with abdominal pain or growth delay, accompanying anorexia, change in diet, diarrhea or extraintestinal manifestations should raise the possibility of Crohn's disease. If fecal leukocytes are found in a patient with hematochezia, inflammatory/infectious causes should be considered. Although 20% of patients with Crohn's disease may have a normal ESR, if it is abnormal, this non-specific marker of inflammation may have relevance.

Table 23.6 Differential diagnosis of Crohn's disease

Symptoms

Differential diagnosis

Constitutional recurrent fever, malaise, pallor

Intestinal abdominal pain

collagen vascular disease, infection, malignancy, especially lymphoma lactose intolerance, constipation, peptic ulcer disease, Helicobacter pylori, irritable bowel syndrome or psychosocial stress

diarrhea

infectious colitis/enteritis (Salmonella, Shigella, Campylobacter, Yersinia); immunodeficiency (HIV, primary immune deficiency)

heme-positive stool/hematochezia

ulcerative colitis, infectious colitis including Shigella, Salmonella, Campylobacter, Escherichia coli O157:H7 and amebiasis, Clostridium difficile colitis, CMV colitis, vasculitis, Henoch-Schönlein purpura; juvenile polyp, Meckel's diverticulum, fissure, hemorrhoid

fever, acute severe abdominal pain

appendicitis, diverticulitis, intestinal perforation

perianal disease

histiocytosis, immunodeficiency

Abnormal liver profile

viral hepatitis, toxin, cholelithiasis

Abnormal pancreatic enzymes

idopathic pancreatitis, familial pancreatitis, cystic fibrosis

Growth failure

celiac disease, cystic fibrosis, endocrinopathy (thyroid, adrenal, pituitary, especially growth hormone), anorexia nervosa,

Pubertal delay

anorexia nervosa; bulimia; chromosomal abnormality

Arthritis

juvenile rheumatoid arthritis, acute rheumatic fever

CMV, cytomegalovirus

Findings on physical examination such as pallor and abdominal tenderness are most often not specific for Crohn's disease, but abdominal mass, aphthoid oral ulcers, erythema nodosum, pyoderma gangrenosum, digital clubbing, arthritis, or perianal skin tags are highly suggestive of Crohn's disease.

Laboratory studies

A number of laboratory tests can offer useful and supportive information in facilitating diagnosis, although they are generally non-specific. An initial screening evaluation with CBC with differential, platelet count, ESR, serum albumin, stool hemoc-cult test, and stool culture are often obtained. Serum iron studies and serum levels of vitamins A, E, B12 and folate can be helpful in assessing specific nutritional deficiencies.

Serological markers

Several serological markers have been reported to facilitate the diagnosis of IBD and in distinguishing between Crohn's disease and ulcerative colitis. Although these tests may have benefit in some clinical situations, the diagnosis remains to be determined by clinical-pathological criteria. Atypical perinuclear antineutrophil cytoplasmic antibodies (atypical P-ANCA, i.e. not directed against myeloperoxidase) can be detected in 60-80% of adult patients with ulcerative colitis and 10-20% of adult patients with Crohn's disease.138-140 In children with IBD, a positive test for P-ANCA and a negative test for anti-Saccharomyces cerevisiae antibody (ASCA) are indicative of increased likelihood of ulcerative colitis rather than Crohn's disease (sensitivity 57%, specificity 97%).139 Conversely, a negative P-ANCA test and a positive ASCA test in children with IBD are suggestive of Crohn's disease (sensitivity 49%, specificity 97%). The relatively low sensitivities of these serological markers for establishing a diagnosis of Crohn's disease and ulcerative colitis limit their widespread clinical utility.103 Antibody against Escherichia coli outer membrane porin (anti-OmpC antibody) has been reported as a potential serological marker for Crohn's disease. It is a curious finding that the markers that are associated with Crohn's disease are related to a host response to luminal organisms

(i.e. yeast and bacteria). As experience increases in the pediatric population with the relationship between phenotype and serological markers, they may become more clinically relevant.

Radiographic studies

Barium upper gastrointestinal series with small-bowel follow-through is a useful tool in diagnosing gastroduodenal and ileal involvement of Crohn's disease (Figure 23.3). Radiographic features in patients with Crohn's disease include narrowing of the lumen of the small intestine or colon with nodularity and ulceration, a 'string' sign when luminal narrowing becomes more advanced or with severe spasm, a cobblestone appearance, fistu-lae and abscess formation, and separation of bowel loops, a manifestation reflecting the transmural inflammation and bowel wall thickening. Antral narrowing and segmental structuring of the duodenum can be seen with gastroduodenal Crohn's disease.

Air-contrast barium enema may be helpful in detecting colonic lesions such as ulcers, strictures and fistulae, but these colonic radiographs have been largely replaced by colonoscopy. In specific clinical situations, such as a distal stricture that does not permit visual inspection of the more proximal colon, virtual colonoscopy may be of benefit. Inflammation limited to the colon may make it difficult to distinguish ulcerative colitis from Crohn's colitis; however, radiographic disease in the small intestine, stomach or esophagus strongly supports a diagnosis of Crohn's disease.

Computerized tomography (CT) scans have become extremely valuable in the assessment of the child with established Crohn's disease who presents with abdominal pain or fever. The use of oral, rectal and or intravenous contrast increases the likelihood of finding a fistula, stricture or abscess. For the child with perianal disease, a careful CT scan with narrow cuts may identify a small perirectal abscess.

Scintigraphy

Scintigraphy with the 99mTc hexamethyl, propylene amino oxime (HMPAO)-labeled leukocyte scan (99mTc white blood cell (WBC) scan) has been

Figure 23.3 (a) Axial computerized tomography (CT) images with intravenous and oral contrast revealing abnormal mucosal thickening of the cecum with abnormal enhancement. Numerous enlarged mesenteric lymph nodes are present (arrow). (b) This 15-year-old child with Crohn's disease developed a large abscess in the anterior abdominal wall (arrow).(c) Markedly narrowed terminal ileum with ulcerations seen on a barium study (arrowhead). The same small bowel loop is seen on a coronal reformatted CT image (white arrow). (d) Small fistula tracks are seen extending from a thickened, inflamed terminal ileum to the ascending colon (arrow). (Courtesy of Dr Sudha Anupindi).

Figure 23.3 (a) Axial computerized tomography (CT) images with intravenous and oral contrast revealing abnormal mucosal thickening of the cecum with abnormal enhancement. Numerous enlarged mesenteric lymph nodes are present (arrow). (b) This 15-year-old child with Crohn's disease developed a large abscess in the anterior abdominal wall (arrow).(c) Markedly narrowed terminal ileum with ulcerations seen on a barium study (arrowhead). The same small bowel loop is seen on a coronal reformatted CT image (white arrow). (d) Small fistula tracks are seen extending from a thickened, inflamed terminal ileum to the ascending colon (arrow). (Courtesy of Dr Sudha Anupindi).

used as an alternative, non-invasive diagnostic test to determine the extent and distribution of inflammation in children with IBD.142-144 In one study,141 the result of the 99mTc WBC scan correlated with histological findings on endoscopic and colono-scopic biopsies in 128 of 137 children. The sensitivity and specificity were 90% and 97%, respectively.141 Nevertheless, the value of this study for diagnosis is limited.

Endoscopic studies and histologic features

Compared with the continuous distribution of ulcerative colitis, Crohn's disease is characteristically segmental, with areas of sparing throughout the intestinal tract; the terminal ileum is the most commonly affected site.103 Data from a study in 389 children and adolescents with Crohn's disease103 revealed that 29% of patients had involvement of the terminal ileum with or without cecal disease, 9% had more isolated proximal (ileal or jejunal) disease, 42% had ileocolonic inflammation and 20% had only colonic involvement.

Endoscopic examination is an important diagnostic tool for Crohn's disease and colonoscopy is the most effective test to determine whether the colon is affected. Crohn's disease often spares the rectosigmoid region, but this pattern of involvement may also be seen in early ulcerative colitis, especially in young patients. The colonoscopic features of Crohn's disease range from subtle focal aphthoid ulcerations adjacent to areas of normal appearing mucosa (Figure 23.4) to diffuse areas of edema and ulceration that create a polypoid mucosa and give a cobblestone appearance (Figure 23.5). Discontinuous colonic involvement with intervening normal appearing mucosa, often referred to as skip areas, is a key feature of Crohn's disease. Deep linear ulcerations may evolve into mucosal bridges with relatively normal-appearing mucosa traversing ulcers (Figure 23.6). Nonspecific gastritis and duodenitis may be seen in patients with Crohn's disease on esophagogastro-duodenoscopy, but histological findings are often most helpful in establishing a diagnosis.

Mucosa that appears grossly normal may reveal abnormalities on histological examination. Edema and an increase in mononuclear cell density in the lamina propria are relatively non-specific findings.103

Positive Asca Negative Colonoscopy
Figure 23.4 Focal aphthous lesion in Crohn's disease with surrounding area of erythema (arrow).
Figure 23.5 Cobblestone appearance (arrow) and mucosal ulcerations with mucopurulent exudate of the colon in Crohn's disease. (Courtesy of Dr Esther J. Israel).

In the early phases of Crohn's disease, microscopic changes may resemble an infectious colitis with infiltration of the crypts by polymorphonuclear leukocytes (cryptitis or crypt abscesses), and distortion of crypt architecture103 (Figure 23.7). Focal

Bridging Tracks Crohn Colitis
Figure 23.6 Ulceration with mucosal bridging (arrows) caused by undermining ulcerations of the colon in Crohn's disease. (Courtesy of Dr Esther J. Israel).
Figure 23.8 (a) Focal ileitis in Crohn's disease (arrow) (low-power view). (b) Ileitis in Crohn's disease (highpower view) demonstrating neutrophilic infiltrate into the mucosa (arrow). (Courtesy of Dr Gregory Lauwers).
Figure 23.7 Active colitis in Crohn's disease (arrow) with area of relatively preserved mucosa without mucin depletion. (Courtesy of Dr Gregory Lauwers).

ileitis is characteristic of Crohn's disease (Figure 23.8). The presence of fibrosis and histiocytic proliferation in the submucosa suggests Crohn's disease. The pathological hallmark of Crohn's inflammation is focal inflammation or transmural extension involving all layers of the bowel wall. Non-necrotizing granulomas are seen in 60% of surgical specimens and 20-40% of mucosal biopsies145'146 (Figure 23.9). Microscopic focal enhancing lesions in the stomach (Figure 23.10) were thought to be indicative of Crohn's disease, but they can be seen in ulcerative colitis as well. However, they are supportive of a chronic inflammatory process.

Figure 23.9 Focal granuloma (arrow) in the colon of a child with Crohn's disease. (Courtesy of Dr Gregory Lauwers).
Figure 23.10 Focal enhancing lesions of the stomach in a patient with Crohn's disease. (Courtesy of Dr Gregory Lauwers).
Natural Arthritis Pain Remedies

Natural Arthritis Pain Remedies

It's time for a change. Finally A Way to Get Pain Relief for Your Arthritis Without Possibly Risking Your Health in the Process. You may not be aware of this, but taking prescription drugs to get relief for your Arthritis Pain is not the only solution. There are alternative pain relief treatments available.

Get My Free Ebook


Post a comment