The diagnosis and treatment 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 diagnostic knowledge related to IBD. The incidence and prevalence of CD is on the rise worldwide today. CD most often occurs in young adults, with a peak age of onset of 18-35 years and slightly more males than females. CD can occur anywhere in the gastrointestinal tract from the mouth to the anus, often in a segmental or discontinuous distribution.
1. Which patients should be considered for Crohn’s disease?
The clinical presentation of CD is diverse. Patients do not necessarily exhibit all the symptoms.
(1) Gastrointestinal manifestations: diarrhea and abdominal pain, which may include bloody stools.
(2) Systemic manifestations: weight loss, fever, loss of appetite, fatigue, anemia, etc. Growth retardation is seen in adolescent patients.
(3) Complications: fistula, abdominal abscess, intestinal stricture and obstruction, perianal lesions (perianal abscess, perianal fistula, skin fistula, anal fissure, etc.) and, less commonly, gastrointestinal hemorrhage and acute perforation.
(4) Extra-intestinal manifestations: skin and mucous membrane manifestations (such as oral ulcers, erythema nodosum and gangrenous pyoderma), joint damage (peripheral arthritis, spinal arthritis), ocular lesions (iritis, scleritis, 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 abscess and perianal fistula can be the first presentation in a small number of patients with CD, and the principles of treatment are different from those of common anal fistula and should be given high priority.
2. What is the first step in establishing the diagnosis?
Colonoscopy (should enter the terminal ileum) and biopsy is the first step to establish the diagnosis. Microscopy generally shows segmental, asymmetric manifestations of various mucosal inflammations, with characteristic endoscopic manifestations of discontinuous lesions, longitudinal ulcers and pebble-like 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. In contrast to microscopic mucosal biopsy, surgical resection specimens can be seen for more lesions, such as segmental transmural inflammation, lacunar ulcers, aphthous ulcers, abnormal crypt structures, and lymphoid follicle formation.
3.What other tests should be done after colonoscopy?
Whether colonoscopy confirms the diagnosis of CD or suspected CD, the involvement of the small intestine and upper gastrointestinal tract should be clarified. CT or magnetic resonance intestinal imaging (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 (inflammatory active or fibrous strictures), 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.
4.Which 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 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 type CD is sometimes difficult to distinguish from UC and can be clinically diagnosed as IBD type to be determined (IBDU). And undetermined colitis (IC) refers to the pathological examination after colon resection still can not distinguish between UC and CD.
5.How should the diagnosis be made?
Based on the exclusion of other diseases, the diagnosis can be made according to the following points.
(1) With clinical manifestations can be clinically suspected, arrange further examination;
(2) With both colonoscopy or small bowel microscopy (lesions confined to the small intestine) and imaging (CTE or MRE, or barium small bowel imaging if not available) features, the clinical diagnosis can be made;
(3) If the biopsy suggests characteristic changes of CD and can exclude intestinal tuberculosis, the clinical diagnosis can be made;
(4) If surgical resection specimens (including resection of intestinal segments and lymph nodes near the lesion) are available, pathological confirmation of the diagnosis can be made according to the criteria;
(5) For the first diagnosed cases without pathological confirmation, the clinical diagnosis can be made after more than 6 to 12 months of follow-up, based on the response to treatment and changes in 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 8-12 weeks, and then differentiated.