Fig. 15.1
“Fat creeping” phenomenon (arrow) in the small bowel in a patient with Crohn’s disease
Aphthoid lesions, fissural ulcerations, cobblestone pattern
Fistula
Rectum is typically spared
Perianal lesions
Microscopic features:
Transmural chronic inflammation with lymphoid aggregates
Widening of the submucosa with edema, lymphangiectasia, and submucosal fibrosis
Neuronal hyperplasia, ganglionitis
Transmural fissures and fistula
Noncaseating epithelioid granulomas (high specificity but low sensitivity for diagnosis of Crohn’s disease, are found in 20 % of biopsies and >60 % of resected bowel specimens)
Granulomatous lymphadenitis
15.3 Clinical Manifestations and Symptoms
CD can affect the entire gastrointestinal tract, from the mouth to the anus (see Table 15.1 for a distribution of CD). The most commonly affected part of the bowel is the ileocecal region (60–70 %). Segmental or general colitis and anorectal disease occur in 20–30 % of patients, often in combination.
Terminal ileum | 40–50 % |
Ileocolon | ~20 % |
Colon | ~30 % |
Upper gastrointestinal tract | ~5 % |
Anorectal disease | 20–30 % |
The clinical symptoms depend on the affected bowel and the phenotype. Because the inflammation is typically segmental and may affect the entire gastrointestinal tract, symptoms are predominantly determined by the part of bowel or organ involved. Three phenotypes, which determine clinical behavior, can be differentiated according to the Montreal classification: without stricture formation, nonpenetrating (B1); stricturing (B2); or penetrating (B3). Category B3 includes a subcategory of perianally penetrating (B3p). Most patients initially present with a B1 phenotype, and about half of patients progress to a more aggressive phenotype within 20 years after the initial diagnosis. However, the data and clinical experience seem to question this rigid differentiation, as there is a considerable overlap between these phenotypes: patients often present with both a stricture and a fistula, where the latter is the potential cause of the stenosis or in turn occurs as a consequence of a more distal stenosis. Interenteric fistulas and luminal stenosis are often combined, especially in conglomerate tumors of primarily inflamed bowel and secondary affected adherent bowel.
Stenosis typically presents as acute fibrotic stenosis, which is potentially reversible after medical treatment, or as chronic fibrotic stenosis. In both cases patients suffer from abdominal cramps, especially after eating; pain; and abdominal distension, potentially progressing to subileal obstruction or complete bowel obstruction. Patients also often present with diarrhea – the most common clinical symptom in CD – as a result of either bacterial overgrowth before a stenosis, malabsorption (bile acids in the terminal ileum), or the inflammation itself. This situation, sometimes in combination with occult bleeding, can result in anemia. Furthermore, patients are often malnourished and anorectic. When the transmural inflammation progresses into neighboring tissue, fistulas can occur (Table 15.2, Fig. 15.2). These in turn can trigger abscesses, which may present as pain (mostly dull, noncolicky), fever, or even full-blown sepsis. Conglomerate inflammatory tumors may be palpable as a mass.
Table 15.2
Types of fistula in Crohn’s disease
Type | Clinical symptoms | Indication for surgery |
|---|---|---|
Interenteric | Often asymptomatic | Relative or no indication (except for a high fistula with functional short-bowel syndrome) |
Short-bowel syndrome (e.g., jejunocolic fistula) | ||
Part of a “conglomerate tumor” | ||
Enterocutaneous | Oligosymptomatic | Depends on symptoms |
Painful, skin irritation | Absolute | |
Retroperitoneal (“blind ending”) (Fig. 15.5a, b) | Asymptomatic | |
Ureteral stenosis | ||
Sepsis (smoldering) | ||
Bone affected (septic spondylitis or arthritis) | ||
Enterovesical | Urinary tract infections | Absolute |
Pneumaturia | ||
Enterovaginal | Often oligosymptomatic | Depends on symptoms, relative |
Vaginal passage of gas, stool, or pus | ||
Vaginal discharge | ||
Recurrent vaginal or urinary tract infections | ||
Perianal | Oligosymptomatic | Depends on symptoms, relative |
Pain | ||
Secretion |
Fig. 15.2
Ileocolic fistula (arrow) in Crohn’s disease of the ileocecal region
15.3.1 Extraintestinal Manifestations
Extraintestinal manifestations and associated diseases occur in about 20–40 % of patients and depend on the activity of the CD (Table 15.3). Therefore treatment of the underlying disease should primarily be intensified. Anemia is the most commonly associated disease, mostly because of an iron deficiency caused by chronic inflammation, and less frequent as a result of intestinal bleeding or a lack of vitamin B12 (ileal inflammation/stenosis or loss of ileum after resection). The second most commonly afflicted tissues are the joints, where peripheral and axial arthropathy are generally differentiated. Eyes are involved in 2–13 % and the skin in 2–15 %. Sclerosing cholangitis usually only occurs in patients with Crohn’s colitis. Pancreatitis develops in up to 4 % of patients, but this is often a result of the side effects of medication (azathioprine in 3–5 %) and cholecystolithiasis than from direct inflammation of the duodenum and papilla of Vater or the pancreatic parenchyma.
Table 15.3
Extraintestinal manifestations and associated diseases in Crohn’s disease
Location | Type |
|---|---|
Blood | Anemia |
Thrombophilia | |
Joints | Sakroiliitis |
Peripheral arthritis | |
Ankylosing spondylitis | |
Eyes | Uveitis |
Episcleritis | |
Bones | Osteoporosis/osteopenia |
Skin | Erythema nodosum |
Pyoderma gangrenosum | |
Thorax | Pleuritis |
Myocarditis | |
Kidneys | Amyloidosis |
Nephrolithiasis | |
Pancreas | Pancreatitis |
Hepatobiliary tract | Cholecystolithiasis |
Primary sclerosing cholangitis | |
Cholangiocarcinoma | |
Autoimmune hepatitis |
15.3.1.1 Disease Activity and Classification
Disease pattern, activity, and severity are classified several ways, and these are worthwhile in studies [3]. But in clinical routine these classifications, such as the Crohn’s Disease Activity Index (CDAI) or the pediatric CDAI (PCDAI) are generally too complex. The CDAI is a validated composite score grading the severity of CD based on the following clinical parameters measured over 7 days: number of soft or liquid stools, use of antidiarrheal medication (0 or 1), abdominal pain (0–3), general well-being (0–4), number of extraintestinal manifestations, abdominal mass (0, 2, or 5), hematocrit (percentage decrease from expected), and body weight (percentage decrease from expected). The scores achieved for each parameter are multiplied by a predefined factor and summarized to provide a final score, which ranges from 0 to approximately 600. A CDAI score below 150 is generally considered to mean quiescent disease, whereas a score above 450 generally signifies very severe disease.
The Harvey-Bradshaw index is a simplified disease activity index. It consists only of clinical parameters, but it has also not really been implemented in clinical practice.
Clinical disease activity can be categorized as mild, moderate, or severe (Table 15.4), although these groups are not precisely defined entities. Most studies consider moderate disease activity (CDAI >220 in adults and PCDAI ≥30 in children) as a prerequisite for inclusion in trials. But because of the high remission rate in the placebo groups in recent studies, a C-reactive protein concentration >10 mg/L is now often also required.
Table 15.4
Grading of disease activity in Crohn’s disease (European Crohn’s and Colitis Organisation guidelines, version 4)
Mild | Moderate | Severe |
|---|---|---|
Equivalent to a CDAI of 150–220 | Equivalent to a CDAI of 220–450 | Equivalent to a CDAI >450 |
Patient is ambulatory, eating and drinking, and has <10 % weight loss No features of obstruction, fever, dehydration, abdominal mass, or tenderness | Intermittent vomiting or weight loss >10 % | Cachexia (body mass index 18 kg/m2) or evidence of obstruction or abscess |
No overt obstruction | Persistent symptoms despite intensive treatment | |
CRP is usually higher than the upper limit of normal | Treatment for mild disease is ineffective or there is a tender mass | CRP increased |
CRP is higher than the upper limit of normal |
The following classification into remission, response, and relapse is of value in studies:
Remission: reduction of the CDAI to <150 points, or, in children, of the PCDAI to ≤10 points.
Relapse: reduction of the CDAI by at least 100 points; in children, of the PCDAI by at least 12.5 points.
Recurrence: reoccurrence of symptoms after a remission with a >70-point increase in the CDAI (PCDAI, ≥12.5 points) and an overall CDAI >150, given there was a remission beforehand, with a CDAI of <150 points.
Furthermore, guidelines distinguish between localized and extensive disease:
Localized disease: intestinal CD affecting <30 cm, usually in an ileocecal location (but also may include more proximal small or large bowel)
Extensive disease: intestinal CD affecting >100 cm, whatever the location. This applies to all inflammation in discontinuous segments.
Obviously, there is a wide area between 30 and 100 cm, but these somewhat pragmatic definitions are of value for medical and especially surgical decision making (roughly, the more bowel affected, the higher the threshold to operate).
15.3.1.2 Diagnostics
There is no single gold standard method to diagnose CD. The diagnosis is based on the clinical picture, the course of the disease, and the combination of diagnostic modalities, including laboratory workup, endoscopy, histology, and radiology.
15.3.2 Differential Diagnosis
In acute lower-quadrant pain, acute appendicitis and yersiniosis are the most important differential diagnoses. Granulomatous chronic intestinal inflammations can also be caused by sarcoidosis or tuberculosis, especially outside Western Europe. Malignant lymphomas and small-bowel cancers occasionally are the reason for small-bowel stenosis and a “conglomerate.” The major differential diagnoses in Crohn’s colitis are ulcerative colitis, infectious colitis (including pseudomembranous colitis), and irritable bowel syndrome.
15.3.3 Laboratory
Initial laboratory testing, apart from a standard workup (e.g., full blood count, urea) should include markers of inflammation (C-reactive protein). Fecal calprotectin and lactoferrin can be used to differentiate inflammation from functional complaints, as they are very sensitive markers for bowel inflammation. Calprotectin, for example, has a positive predictive value of 85–90 % in distinguishing inflammatory bowel disease from irritable bowel syndrome. However, these tests are not very specific for CD and are therefore mostly useful during patient follow-up. Albumin is a valuable parameter for nutritional status, especially preoperatively, since a low concentration is correlated with a higher risk of complications [5].
15.3.4 Endoscopy
Ileocolonoscopy and random biopsies from the terminal ileum and each colonic segment should be done to look for microscopic evidence of CD to establish the diagnosis (Fig. 15.3). Moreover, the upper gastrointestinal tract also needs to be investigated by endoscopy to rule out Crohn’s lesions there or other diagnoses. Endoscopy is of importance in monitoring treatment and also postoperatively, as newer studies imply a better outcome in patients treated early and aggressively on the basis of early mucosal changes on endoscopy [6].
Fig. 15.3
Endoscopic view of a stenosis with a cobblestone appearance in the distal ileum of a patient with Crohn’s disease
15.3.5 Imaging
High-resolution ultrasound has an important role in the acute setting, especially to detect fistulas, stenosis, and abscesses. It is also useful to monitor bowel inflammation during treatment.
A plain radiograph is of value in emergency situations, such as bowel obstruction and perforation.
High-resolution magnetic resonance imaging (MRI) or computed tomography (CT) enterography or enteroclysis have the highest diagnostic accuracy for detecting intestinal involvement in CD and especially extramural complications such as fistulas and abscesses. MRI and CT and should be performed during the primary workup of patients with a high suspicion of CD. As MRI has no risk of radiation exposure, it should be preferred whenever possible (Figs. 15.4 and 15.5). CT is generally preferred when an intervention is likely (e.g., abscess drainage; Fig. 15.6).
Fig. 15.4
Inflammatory stenosis in the distal ileum (wall thickening; white arrow) with prestenotic dilatation (black arrow)
Fig. 15.5
(a, b) Inflammatory stenosis in the distal ileum (wall thickening; white arrow) with a blind-ending fistula to the retroperitoneum (black arrow) (a axial image, b coronal image)
Fig. 15.6
Large pelvic abscess in ileocecal Crohn’s disease (arrow)
In rare cases where the standard imaging techniques are negative but there still is a high clinical suspicion of CD, small-bowel capsule endoscopy can be used to clarify the diagnosis. Double-balloon enteroscopy is only indicated in cases where biopsies (e.g., to exclude malignancy) or therapeutic procedures (e.g., dilatation of a stenosis) are warranted.
In perianal disease, MRI is the imaging modality of choice because it is very accurate. Endosonography is an alternative and is probably as good as MRI if performed by an experienced examiner. But its use is limited because of access (anal stenosis) and pain issues, especially in severe perianal disease.
15.3.5.1 Therapy
Treatment in CD is primarily conservative [7, 8]. However, there are special situations where surgery can be considered (e.g., isolated short-segment ileocecal inflammation) or must be implemented (emergencies) as the primary treatment. The choice of drug in conservative treatment greatly depends on disease activity, site, and accompanying complications (e.g., stenosis, abscess). Obviously, patients need to be counseled with regard to the immense harm of smoking in CD. (Smoking cessation is more effective than any medication to prevent postoperative recurrence!)
Steroids should not be given over a longer period of time because of their side effects and because they are not effective in maintaining remission.
15.4 First-Line Treatment
15.4.1 Ileocecal CD
15.4.1.1 Mildly Active
Budenoside 9 mg/day is the treatment of choice, and about 50–70 % of patients will go into remission within 8–12 weeks. Mesalazine is considerably less effective but can be used. Merely symptomatic therapy is also viable as between 20 % and up to 40 % of patients go into spontaneous remission.
15.4.1.2 Moderately Active
Budenoside 9 mg/day or systemic steroids (1 mg/kg/day), with the addition of antibiotics if needed (septic complications), is the treatment of choice. This is effective in up to 90 % of patients within 6 weeks.
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