| disease | Crohn's Disease |
| alias | Granulomatous Enteritis, Crohn, IBD, Localized Enteritis, Inflammatory Bowel Disease, Crohn's Disease, Segmental Enteritis |
Crohn's disease, also known as regional ileitis, regional enteritis, segmental enteritis, and granulomatous enteritis, is an inflammatory bowel disease of unknown cause. Together with chronic nonspecific ulcerative colitis, these conditions are collectively referred to as inflammatory bowel disease (IBD). Crohn's disease can occur in any part of the gastrointestinal tract, but it most commonly affects the terminal ileum and the right colon. The main symptoms include abdominal pain, diarrhea, and intestinal obstruction, along with extraintestinal manifestations such as fever and nutritional disorders. The disease often follows a prolonged and relapsing course, making it difficult to cure completely.
bubble_chart Epidemiology
This disease is distributed worldwide and is less common in China compared to Europe and America. Over the past decade or so, it has become more frequently encountered in clinical practice. According to domestic literature reports from 1950 to 1982, a total of 523 cases were confirmed by surgery and pathology, while from 1987 to 1993, 625 cases were reported. There is no significant difference between genders. It can occur at any age, but young and middle-aged individuals account for more than half of the cases.
The cause of the disease remains unclear and may result from the combined effects of multiple factors, with immune abnormalities, infections, and genetic factors appearing to be more closely related.
(1) Immunity: Both humoral and cellular immunity in patients are abnormal. In more than half of the cases, colonic antibodies, circulating immune complexes (CIC), and elevated complement C2 and C4 can be detected in the blood. Using immunoenzyme labeling, antigen-antibody complexes and complement C3 can be observed in the affected tissues. The occurrence of arthralgia in Crohn's disease is also related to local damage caused by the deposition of CIC. In tissue culture, the patient's lymphocytes exhibit cytotoxicity and can kill normal colonic epithelial cells; when the diseased intestinal segment is removed, the cytotoxic effects disappear. The patient's macrophages also collaborate with T cells and antibody-mediated cytotoxicity to attack target cells and damage tissues. Leukocyte migration inhibition tests show abnormal reactions, indicating cell-mediated delayed hypersensitivity; the subcutaneous node tuberculin test shows a diminished response; the dinitrochlorobenzene (DNCB) test is often negative, all supporting the notion of impaired cellular immune function. In recent years, certain cytokines, such as IL-1, IL-4, IL-8, IL-10, interferon-gamma, and tumor necrosis factor-alpha, have been found to be associated with the pathogenesis of inflammatory bowel disease. For example, serum and mucosal IL2
levels are elevated in patients with active inflammatory bowel disease, and the use of IL2 can worsen the condition, while anti-IL2 receptor antibodies can improve it. Some believe Crohn's disease is an autoimmune disorder.(2) Infection: Using specific DNA probes and PCR methods, Mycobacterium paratuberculosis (MP) has been detected in two-thirds of Crohn's disease patients. However, anti-MP treatment has shown limited efficacy, and this bacterium is also present in the intestinal walls of healthy individuals. Therefore, the relationship between the disease and MP infection remains uncertain, though it may be linked to relapse induction. Additionally, recent studies suggest no association between Crohn's disease and viral or chlamydial infections.
(3) Genetics: Genetic factors have received significant attention in recent years. Studies on monozygotic and dizygotic twins show that the co-occurrence of Crohn's disease is much higher than that of ulcerative colitis. The incidence is higher among North American Jews compared to Black individuals, with a positive family history exceeding 10%. The shared environment, diet, and lifestyle among family members cannot be entirely ruled out as contributing factors. Recent findings suggest chromosomal instability in patients with this disease.
bubble_chart Pathological Changes
Crohn's disease is a proliferative inflammatory lesion that affects all layers of the intestinal wall and involves the mesentery and regional lymph nodes. The lesions are confined to the small intestine (mainly the terminal ileum) in 30% of cases, to the colon in another 30%, and involve both the ileum and right colon in 40%. Crohn classified the pathological changes into the acute inflammatory phase, ulcer formation phase, stricture phase, and fistula formation phase (perforation phase). The lesions are segmentally distributed, alternating with normal intestinal segments, with clear boundaries, exhibiting the characteristic "skip area." In the acute phase, the intestinal wall is primarily affected by edema and inflammation; in the chronic phase, the intestinal wall thickens and becomes rigid, with the affected segment taking on a tubular shape, and the proximal segment dilating due to stricture. Typical mucosal lesions include: ① Ulcers: initially small and superficial, later developing into longitudinal or transverse ulcers. Deep longitudinal ulcers penetrating the intestinal wall form characteristic fissures, typically distributed along the mesenteric side. Abscesses may form in the intestinal wall. ② Cobblestone nodules: caused by submucosal edema and cellular infiltration forming small island-like protrusions, combined with fibrosis and scar contraction from healed ulcers, giving the mucosal surface a cobblestone appearance. ③ Granulomas: composed of epithelioid cells, often accompanied by Langhans cells but without caseous necrosis, distinguishing them from subcutaneous nodules. Intestinal granulomas are a response to inflammatory stimuli and are not unique to Crohn's disease; moreover, 20–30% of cases lack granulomas, so the term "granulomatous enteritis" is inappropriate. ④ Fistulas and abscesses: fissures in the intestinal wall are essentially penetrating ulcers, leading to adhesions and abscesses between intestinal segments or between intestinal segments and adjacent organs or tissues (such as the bladder, vagina, mesentery, or retroperitoneal tissues), forming internal fistulas. If an intestinal segment penetrates the intestinal wall and extends through the abdominal wall or perianal tissue to the exterior, an external fistula is formed.
The manifestations are diverse and are related to the location, extent, severity, duration of intestinal lesions, and the presence of complications. Typical cases usually have a slow onset in youth, with a disease course often lasting from several months to years. The active phase and the {|###|}stage of remission vary in duration and alternate with each other, showing progressive deterioration during recurrent episodes. A few cases have an acute onset, with symptoms such as high fever, toxemia, and acute abdomen. The entire course is short, abdominal symptoms are severe, and there are often serious complications. Occasionally, the initial symptoms may be extraintestinal manifestations such as perianal abscess, fistula formation, or {|###|}arthralgia, while abdominal symptoms are not obvious. The main manifestations of this disease are as follows.
(1) {|###|}diarrhea: Common (70–90%). Most patients have 2–6 bowel movements per day, often without pus or blood in the stool; if the rectum is involved, there may be a sense of {|###|}tenesmus.
(2) {|###|}abdominal pain: Common (50–90%). It is mostly located in the right lower abdomen, related to lesions in the terminal {|###|}ileum. Postprandial {|###|}abdominal pain is associated with the gastrocolic reflex. Inflammation of the intestinal submucosa stimulates pain receptors, causing muscle layer contraction and stretching of the intestinal wall, leading to {|###|}severe pain. Involvement of the serosa, perienteric abscess, intestinal adhesions and obstruction, intestinal perforation and acute peritonitis, as well as toxic megacolon, can all cause {|###|}abdominal pain. Only 1.8% of cases present with acute appendiceal Crohn’s disease as the initial symptom, but general acute {|###|}appendicitis may occur in 14–50% of Crohn’s disease cases during the course of the illness.
(3) {|###|}fever: Occurs in 5–40% of cases. Active intestinal inflammation and toxin absorption from tissue destruction can cause {|###|}fever. It is usually moderate or low-grade and often intermittent. In acute severe cases or those with suppurative complications, high fever, {|###|}shiver, and other toxemic symptoms may occur.
(4) Abdominal mass: About one-third of cases present with an abdominal mass, most commonly in the right lower abdomen and around the umbilicus. Intestinal adhesions, thickening of the intestinal wall and mesentery, mesenteric lymphadenopathy, internal fistula formation, and intra-abdominal abscesses can all cause abdominal masses, which are easily confused with abdominal {|###|}subcutaneous nodes and tumors.
(5) {|###|}hematochezia: Compared with ulcerative colitis, fresh blood in the stool is less common and the amount is generally small.
(6) Other manifestations: Include {|###|}nausea, {|###|}vomiting, poor appetite, {|###|}lack of strength, weight loss, anemia, hypoalbuminemia, and other nutritional disorders, as well as extraintestinal manifestations and clinical symptoms caused by complications.
bubble_chart Auxiliary Examination
(1) Blood tests, etc. White blood cells are often elevated; red blood cells and hemoglobin are reduced to varying degrees, which is related to {|###|}loss of blood{|###|}, bone marrow suppression, and decreased absorption of iron, folic acid, and vitamin B12. Hematocrit decreases; erythrocyte sedimentation rate increases.
(2) Stool tests Red and white blood cells may be observed; occult blood test may be positive.
(3) Blood generation and transformation tests α1 and α2-globulins increase, blood glycoproteins rise, mucoproteins increase, and albumin decreases. Serum potassium, sodium, calcium, magnesium, etc., may decrease. Plasma prothrombin time is prolonged. Serum lysozyme levels rise, which is related to the release of this enzyme after macrophage destruction.
(4) Intestinal absorption function tests For patients with {|###|}small intestine{|###|} lesions who have undergone extensive intestinal resection or have malabsorption, further evaluation of {|###|}small intestine{|###|} function is recommended (see "Malabsorption Syndrome" for details).
X-ray examination
Gastrointestinal barium meal imaging can reveal lesions and extent of the terminal {|###|}ileum{|###|} or other parts of the {|###|}small intestine{|###|}. Manifestations include inflammatory changes in the gastrointestinal tract, such as fissure-like {|###|}ulcer{|###|}, cobblestone appearance, pseudopolyps, single or multiple strictures, fistula formation, etc., with lesions distributed segmentally. Barium enema aids in diagnosing colonic lesions, and double-contrast barium enema can improve diagnostic accuracy. Abdominal X-ray plain films may show intestinal loop dilation and extraluminal masses.
Endoscopy and biopsy
Endoscopy and mucosal biopsy help detect microscopic and various stages of lesions, such as mucosal {|###|}edema{|###|}, {|###|}ulcer{|###|}, intestinal lumen narrowing, pseudopolyp formation, and cobblestone-like mucosal appearance. Lesions are distributed in a skip pattern. Transoral {|###|}small intestine{|###|} mucosal biopsy is significant for diagnosing Crohn's disease in the duodenum and upper jejunum.
Diarrhea, abdominal pain (especially chronic), and abdominal masses should raise suspicion of Crohn's disease. If intestinal obstruction or perianal lesions are present, X-ray and endoscopic examinations are particularly necessary. Acute ileal Crohn's disease can easily be confused with acute appendicitis, acute hemorrhagic enteritis, and other acute abdominal conditions. Sometimes, it is difficult to differentiate this disease from ulcerative colitis. Recent statistics show that in pathological sections of IBD cases, 5–10% of cases still cannot be definitively diagnosed. It has been reported that ultrasound-guided percutaneous fine-needle aspiration of abnormal small intestinal walls can aid in differentiation. Using retrograde colonic irrigation ultrasound, 89% of Crohn's disease cases can be distinguished from ulcerative colitis. Crohn's disease cannot be diagnosed solely based on the presence or absence of granulomas.
bubble_chart Treatment Measures
Currently, there is no definitive cure. General supportive and symptomatic treatments are crucial. Strengthening nutrition, correcting metabolic disorders, and improving anemia and hypoalbuminemia are essential. Blood transfusions, plasma, albumin, compound amino acids, or even elemental diets or total parenteral nutrition may be administered when necessary.
(1) Sulfasalazine (SASP) and 5-aminosalicylic acid (5-ASA) are suitable for patients in the chronic phase or mild to moderate (grade II) active phase. SASP is broken down by bacteria in the colon into 5-ASA and sulfapyridine. The latter can cause adverse effects such as gastrointestinal symptoms, leukopenia, rashes, and abnormal semen leading to infertility, while the former is the active component of SASP, primarily reducing inflammation by inhibiting prostaglandin synthesis. The treatment dose is 4–6 g/day, divided into four doses, with effects typically seen in 3–4 weeks. After symptom relief, the dose can gradually be reduced to a maintenance dose of 1–2 g/day, recommended for continuous use over 1–2 years.
(2) Adrenal corticosteroids: Corticosteroids stabilize lysosomal enzymes, reduce capillary permeability, inhibit chemotaxis and phagocytosis, and influence cell-mediated immune responses. They are commonly used for severe or fulminant cases. The treatment dose is prednisone 40–60 mg/day for 10–14 days, with 75–90% of patients experiencing symptom relief. The dose can then be gradually tapered to 5–15 mg/day for maintenance over 2–3 months, though some advocate for 1–2 years. In 10–15% of patients, symptoms may recur after complete discontinuation, necessitating long-term oral prednisone at 10–15 mg/day for control. For those intolerant to oral administration, intravenous hydrocortisone 200–400 mg/day or ACTH 40–60 units/day may be used for 14 days before switching to oral prednisone for maintenance.
(3) Other drugs: For patients unresponsive to sulfonamides or corticosteroids, other immunosuppressants such as azathioprine, 6-mercaptopurine (6MP), cyclosporine, or FK506 may be substituted or added. Immunostimulants like levamisole, interferon, transfer factor, BCG, and immunoglobulins can also be combined. Additionally, metronidazole, broad-spectrum antibiotics, isolated T cells, and monoclonal antibodies may be used, though the efficacy of these drugs varies.
(4) Surgical intervention: Half of the cases will eventually require surgical resection of the affected intestinal segment. Some cases may require reoperation within 5–10 years.
Emergency surgery indications: ① Acute small intestine obstruction; ② Toxic megacolon unresponsive to conservative treatment; ③ Suspected acute appendicitis; ④ Acute intestinal perforation or severe bleeding unresponsive to conservative treatment; ⑤ Intestinal infections uncontrolled by antibiotics.
Elective surgery indications: ① Poor response to medical therapy with persistent intestinal obstruction and abdominal pain, or lack of general improvement; ② Severe adverse drug reactions; ③ Complications such as fistulas, severe perianal lesions, or severe intra-abdominal abscesses; ④ Suspected malignancy.
Surgical approaches: ① Simple lesion resection; ② Rectal, colonic, or subtotal colectomy; ③ Ileostomy.
This disease is mostly chronic and progressive, and although it may resolve on its own, it often recurs. The vast majority of patients can achieve some degree of recovery with appropriate treatment. About half of the patients survive 15 years after onset. Acute severe cases often present with severe toxemia and complications, resulting in a poorer prognosis, with a recent mortality rate of approximately 3–10%. In recent years, it has been found that the cancer rate in Crohn's disease is also relatively high.
More than 40% of cases experience varying degrees of intestinal obstruction, which can recur. Acute intestinal perforation accounts for 10–40%. Conditions such as anal and rectal lesions, fistulas, toxic megacolon, and cancerous changes are relatively rare in China. Crohn's disease can manifest with numerous extraintestinal or systemic sexually transmitted diseases, including arthralgia (inflammation), aphthous ulcers, erythema nodosum, pyoderma gangrenosum, inflammatory eye disease, chronic active hepatitis, fatty liver, gallbladder stones, sclerosing cholangitis and pericholangitis, kidney stones, thrombophlebitis, ankylosing spondylitis, vasculitis, Behçet's disease, amyloidosis, osteoporosis, and clubbing of fingers. Those who develop the disease at a young age may exhibit growth retardation.
When diagnosing this disease, other intestinal infections and lesions, vascular diseases, and tumors should be excluded, such as bacterial dysentery, amoebic dysentery, intestinal tuberculosis, schistosomiasis, as well as enteritis caused by other diseases, colorectal cancer, small intestine lymphoma, fleshy tumors, carcinoid tumors, chronic intestinal fungal infections, and intestinal Behçet's disease.
