The diagnosis and management of Crohn’s disease (CD), like oncology, is increasingly focused on a multidisciplinary and integrated treatment model. Both gastrointestinal surgeons and internists should be aware of the basic diagnosis and treatment of IBD.
The incidence and prevalence of CD is on the rise worldwide, and CD most often occurs in young adults, with a peak age of 18-35 years and slightly more males than females, and can occur anywhere in the gastrointestinal tract from the mouth to the anus, often with a segmental or discontinuous distribution.
CD lacks a gold standard for diagnosis, so how exactly should Crohn’s disease be diagnosed?
Which patients should be considered for possible Crohn’s disease?
The clinical presentation of CD is diverse. Patients do not necessarily exhibit all the symptoms.
Gastrointestinal manifestations: diarrhea and abdominal pain, which may include bloody stools.
systemic manifestations: weight loss, fever, loss of appetite, fatigue, anemia, etc. Growth retardation is seen in adolescent patients.
Complications: fistulas, abdominal abscesses, intestinal strictures and obstruction, perianal lesions (perianal abscesses, perianal fistulas, dermatomes, anal fissures, etc.) and, less commonly, gastrointestinal hemorrhage and acute perforation.
Extra-intestinal manifestations: skin and mucous membrane manifestations (e.g. oral ulcers, erythema nodosum and gangrenous pyoderma), joint damage (peripheral arthritis, spondyloarthritis), ocular lesions (iritis, sclerositis, uveitis), primary sclerosing cholangitis, thromboembolic disease, etc.
In conclusion, diarrhea, abdominal pain and weight loss are common symptoms of Crohn’s disease, and the presence of these symptoms, especially in young patients, should be considered as a possibility of the disease. The disease is highly suspected if accompanied by extraintestinal manifestations or (and) perianal lesions. Perianal abscesses and perianal fistulas can be the first presentation in a small number of patients with CD. The principles of treatment are different from those of common anal fistulas and should be given high priority.
What is the first step in establishing a diagnosis?
Colonoscopy (which should access the terminal ileum) and biopsy is the first step in establishing the diagnosis. The microscopic presentation is usually segmental and asymmetric with various mucosal inflammatory manifestations, with characteristic endoscopic manifestations being discontinuous lesions, longitudinal ulcers and an oval appearance.
Non-caseating granulomas are a histologic hallmark of CD, but not all patients with CD have this type of lesion; only about 30% of patients with CD will present with non-caseating granulomatous lesions. Moreover, non-caseating granulomas can be seen in other diseases such as sarcoidosis and syphilis. Therefore, non-caseating granulomas are not necessary for the diagnosis of CD. As opposed to microscopic mucosal biopsy, surgical resection of the specimen can reveal more lesions, such as segmental transmural inflammation, lacunar ulcers, aphthous ulcers, abnormal crypt structures, and lymphoid follicle formation.
What other tests should be done after colonoscopy?
Whether colonoscopy confirms a diagnosis of CD or suspected CD, the involvement of the small intestine and upper gastrointestinal tract should be clarified. CT or magnetic resonance enterography (CT/MR enterography, CTE/MRE) or small bowel barium angiography and gastroscopy should be routinely performed to understand the inflammatory changes in the intestinal wall, the site and extent of lesion distribution, the presence of strictures and their possible nature (active inflammatory or fibrous strictures), and extra-intestinal complications such as fistula formation, abdominal abscesses or cellulitis. The typical CTE manifestation of active CD is marked thickening of the intestinal wall (>4 mm); marked intensification of the intestinal mucosa with changes in the stratification of the intestinal wall, marked intensification of the inner mucosal and outer plasma rings, and the “target” or “double halo” sign; increased, dilated, and distorted mesenteric vessels The intestinal vessels are enlarged, dilated and distorted, showing the “wooden comb sign”; the corresponding mesenteric fat density is increased and blurred; the mesenteric lymph nodes are enlarged, etc.
If the diagnosis of CD is suspected but colonoscopy and small bowel radiography are negative, capsule endoscopy is performed. For lesions confined to the small intestine suspected to be CD, balloon-assisted small bowel microscopy was performed.
Pelvic MR in the presence of perianal fistula (combined with ultrasound endoscopy or percutaneous perianal ultrasonography if necessary). Abdominal ultrasonography can be used as a primary screening test for suspected abdominal abscesses, inflammatory masses or fistulas.
What diseases should CD be differentiated from?
The most difficult disease to differentiate from CD is intestinal tuberculosis. It can also be difficult to differentiate between those with atypical systemic manifestations of intestinal Behcet’s disease. Other diseases that need to be differentiated include infectious enteritis (e.g., HIV-associated enteritis, schistosomiasis, amebic enteropathy, Yersinia pestis, Campylobacter jejuni, Clostridium difficile, cytomegalovirus, etc.), ischemic colitis, radiation enteritis, drug enteropathy such as non-steroidal anti-inflammatory drugs (NSAIDs), eosinophilic enteritis, rheumatic diseases with prominent intestinal lesions (e.g., systemic lupus erythematosus, primary vasculitis, etc.), intestinal malignant lymphoma, diverticulitis, and diversionary enteritis.
Therefore, routine stool and necessary pathogenic tests, routine blood, serum albumin, electrolytes, erythrocyte sedimentation rate, C-reactive protein, autoimmune related antibodies, etc. should be performed. Fecal calprotectin and serum lactoferrin can be performed as auxiliary indicators when available. Tests to rule out intestinal TB should also be performed: chest X-ray, tuberculin (PPD) test, and gamma-interferon release test (e.g. T-SPOTqTB) when available.
Colonic CD is sometimes difficult to differentiate from UC and can be clinically diagnosed as IBD type undetermined (inflammatory bowel disease unclassified, IBDU). In contrast, indeterminate colitis (IC) refers to those who cannot distinguish UC from CD on pathological examination after colectomy.
How should the diagnosis be made?
Based on the exclusion of other diseases, the diagnosis can be made according to the following points: (1) if clinical manifestations are present, the diagnosis can be clinically suspected and further investigations can be arranged; (2) if the features of colonoscopy or small bowel microscopy (lesions confined to the small bowel) and imaging (CTE or MRE, or barium small bowel imaging if not available) are present, the clinical diagnosis can be made; (3) if biopsy indicates characteristic changes of CD and intestinal tuberculosis can be excluded, the clinical diagnosis can be made; (4) if surgery is performed, the diagnosis can be made. If surgical resection specimens (including resection of intestinal segments and lymph nodes near the lesion) are available, pathological diagnosis can be made according to the criteria; ⑤ For the first diagnosed cases without pathological confirmation, clinical diagnosis can be made after more than 6-12 months of follow-up, judging from the response to treatment and changes in the disease, and in accordance with the natural course of CD. If there is confusion with intestinal tuberculosis, but it tends to be intestinal tuberculosis, it should be treated as intestinal tuberculosis for 8 to 12 weeks, and then differentiated.
How is CD staged?
Montreal staging
Age of diagnosis (A)
A1
≤16 years
A2
17~40 years old
A3
>40 years old
Lesion site (L)
L1
Terminal ileum
L1+L4b
L2
Colon
L2+L4b
L3
Ileum
L3+L4b
L4
Upper gastrointestinal tract
Disease behavior (B)
B1a
Non-stenotic non-penetrating
B1pc
B2
Stenosis
B2pc
B3
Penetration
B3pc
Note: a B1 can develop into B2 or B3 over time; b L4 can coexist with L1, L2, and L3; c p is a perianal lesion and can coexist with B1, B2, and B3
How to determine the severity of the disease?
The Crohn’s Disease Activity Index (CDAI) is used clinically to assess the severity of CD disease activity and to evaluate outcomes, and the CDAI is also widely used in research.
Crohn’s disease (ileocolic type, stenosis + anal fistula, moderate active stage)