Ulcerative colonic arthritis

　　The etiology of ulcerative colonic arthritis is not yet clear, and it is related to the following factors:

　　I. Infection factors:The colonic mucosal inflammatory changes in this disease are similar to many infectious colitis, but bacteria, viruses, or fungi have not been identified in this disease, and there is also no evidence of transmission of the disease among the population. Some people also believe that the disease is caused by Shigella or tissue-invasive amebas, and the long course of the disease may also be due to general non-pathogenic intestinal bacteria, which needs further confirmation.

　　II. Psychoneurological factors:Some believe that dysfunction of the cerebral cortex can lead to autonomic nervous system disorders, causing hyperactivity of intestinal motility, spasm and contraction of intestinal vascular smooth muscle, tissue ischemia, and increased permeability of capillaries, thereby forming intestinal mucosal inflammation, erosion, and ulcers. It is currently believed that this factor may be a secondary manifestation of the disease due to recurrent episodes.

　　三、遗传因素现：已确定本病病人HLA-B27的阳性率显著高于对照组人群。在许多家族中，本病的发病率较高。

　　四、免疫因素：近年来在本病免疫学基础方面的重要发现有：病人血清中存在非特异性抗结肠抗体，其中已鉴定的有，抗肠上皮的黏多糖抗体和抗大肠杆菌多糖成分的抗体。在溃疡性结肠炎病变组织中分离出可与IgG结合的40kD器官特异性蛋白，支持本病是自身免疫病的很强的证据。

　　五、过敏学说：由于少数病人对某种食物过敏，排除食物的过敏或脱敏后，病情即好转或痊愈，故有人提出本病为过敏所致。

　　溃疡性结肠炎性关节炎的局部并发症：

　　一、大量便血

　　便血是溃疡性结肠炎的常见症状之一。大量便血是指在短时间内肠道大量出血，伴有脉搏增快、血压下降和血红蛋白降低，需要输血治疗来缓解病情者。便血量的多少有时虽然难以确切估计，但却是评估病情轻重的指标。在有发热、心动过速、血容量下降时，血细胞比容不能反映贫血程度。引起出血的原因，主要由于溃疡累及血管，此外低凝血酶原血症也是一个重要原因。国外有人统计因出血而行结肠切除的58例中，有37例呈低凝血酶原血症。

　　大量出血的发生率小于5％(1.1％～4.0％)，多见于重症病例，继发于溃疡性结肠炎后的下消化道大出血中国并非罕见。出血后可导致重度贫血。急性出血患者中50％合并有中毒性巨结肠。因此，当溃疡性结肠炎出现大出血时，也应考虑存在中毒性巨结肠的可能性。一般经积极强化内科治疗，可以止血，危及生命者需急诊外科手术。

　　二、中毒性巨结肠

　　中毒性巨结肠是溃疡性结肠炎的一个严重并发症，多发生在重型、暴发型、全结肠炎的患者。据报告，国外发生率为1.6％～13.0％；中国则少见，有报告为2.6％。其死亡率可高达11％～50％。

　　这是由于严重的炎症波及结肠肌层及肌间神经丛，破坏了正常肠道的神经与肌肉调节机制，以致肠壁张力低下，呈节段麻痹，肠内容物和气体大量积聚，从而引起急性结肠扩张，肠壁变薄。各种促使肠腔内压升高或肠肌张力降低的因素均可致结肠扩张。多累及乙状结肠和横结肠，因卧位时横结肠的位置靠前，气体容易积聚之故。结肠扩张，肠壁压力增加，细菌和肠内容物经溃疡进入肠壁和血流，造成菌血症和脓毒血症，也可使结肠进一步扩张。脉管炎、肠肌丛或黏膜下丛的受累可能是扩张不可逆的原因。

　　Some drugs such as anticholinergic drugs (e.g., atropine) or opiate drugs can reduce colonic muscle tone, inhibit intestinal motility, and can induce or worsen toxic megacolon, so they should be used with caution. Laxatives (such as compound benzylpiperazine) and the use of laxatives during bowel preparation may also trigger it. During barium enema (and preparation before enema) or colonoscopy, air injection and catheter manipulation can interfere with blood supply or cause trauma, so these examinations should not be performed in severe cases. Hypokalemia is also a common trigger. But it may also be spontaneous. Other causes of toxic megacolon include infection, such as Campylobacter jejuni, Shigella, Salmonella, and Clostridium botulinum.

　　Clinical manifestations depend on the speed of occurrence, the degree of colonic dilation, the severity of toxicity, and the presence or absence of perforation. Patients often have varying degrees of dehydration, fever, tachycardia, anemia, increased white blood cell count, and even shock. The symptoms of diarrhea, hematochezia, and abdominal pain may sometimes be alleviated. Electrolyte imbalance, anemia, hypoalbuminemia, and toxic neuro-psychiatric symptoms may exist to varying degrees. Severe diarrhea, with more than 10 bowel movements per day, can rapidly worsen, with obvious toxic symptoms, accompanied by abdominal distension, tenderness, rebound pain, and decreased or absent bowel sounds. Abdominal distension is marked, especially when the transverse colon is dilated, often with upper abdominal distension. The upper abdominal flat film shows widened intestinal lumen and disappearance of colonic valves, with the diameter of the transverse colon reaching more than 5 to 6 cm. It is prone to complications such as intestinal perforation and acute diffuse peritonitis.

　　For patients with a short course of disease and their first visit, rectoscopy should be performed to observe for signs of ulcerative colitis locally. Examinations above the rectum are somewhat risky and should be avoided. The use of glucocorticoid steroids may mask the symptoms of colonic dilation, leading to missed diagnosis. Attention should be paid to the timing of surgery, as delaying surgery may increase the mortality rate. The prognosis of this complication is poor.

　　Third, intestinal perforation

　　It is a severe complication of toxic megacolon, mainly caused by acute intestinal perforation due to rapid expansion, thinning of the intestinal wall, circulatory disorders, ischemia, and necrosis. It can also be seen in severe cases, with an incidence reported abroad of about 2.5% to 3.5%, mostly occurring in the left colon, causing diffuse peritonitis. Free perforation without megacolon is extremely rare. Severe shock, peritonitis, and sepsis are the main causes of death. The use of corticosteroids is an important factor in triggering this complication. At the same time, due to the use of corticosteroid hormones, clinical symptoms are often atypical, and free subdiaphragmatic air is only discovered through X-ray abdominal film examination. Therefore, special vigilance is required.

　　Four, Polyps

　　The incidence rate of polyps in this disease is 10% to 40%, and such polyps are called pseudopolyps. So-called pseudopolyps are due to the large amount of hyperplasia of granulation tissue in the late stage, edema of normal mucosal tissue, which causes the normal mucosal surface to protrude and form polyps. Such polyps are pathologically inflammatory polyps. Dikes and Caunsell further divided them into mucosal prolapse type, inflammatory polyp type, and adenomatous polyp type. The inflammatory polyp type is the most common, mostly seen in patients with long-term ulcerative colitis, and the location is related to the scope of inflammation, with the rectum being the most common site, and some believe that the descending colon and sigmoid colon are the most common, followed by a decrease upwards, and some can disappear with the inflammation of the colon. Adenomatous polyps can be transformed from inflammatory polyps, or directly derived from normal mucosa, and are also common in patients with long-term ulcerative colitis, with an incidence rate 3 to 5 times higher than that in the general population. Generally, they are accompanied by varying degrees of atypical hyperplasia. If it is mild atypical hyperplasia, it can be followed up with routine colonoscopy about 1 year; moderate atypical hyperplasia is considered a precancerous lesion and should be followed up; if it is severe atypical hyperplasia, after re-examination and confirmed, it is recommended to remove the polyp surgically. Once adenomas are found, special attention should be paid to the examination of the entire colon to observe the presence of multiple adenomas and accompanying cancer. Due to the widespread use of electrocoagulation resection, all those who can be removed can be removed through colonoscopy to avoid future problems, because canceration mainly comes from adenomatous polyps.

　　Five, Carcinoma

　　It is now generally recognized that the opportunity for the occurrence of colorectal cancer in ulcerative colitis is higher than that in the general population of the same age and gender. The reason is still not very clear. The intrinsic defect of the mucosa or the result of long-term chronic inflammation may be the most important predisposing factor, while environmental, nutritional, and genetic factors may also be important. From the perspective of molecular biology, the process of ulcerative colitis evolving into colon cancer is a process of cumulative mutation of oncogenes and tumor suppressor genes in colonic epithelial cells.

　　Six, Intestinal Stricture

　　In a portion of patients undergoing barium enema examination or colonoscopy, colonic stricture may be observed. The incidence rate is 6% to 10%, mostly occurring in patients with extensive lesions, persistent course, and lasting for 5 to 25 years, and the location is mostly in the left colon, sigmoid colon, or rectum. The cause of the stricture is often not due to fibrous tissue hyperplasia, but due to the formation of inflammatory polyps, thickening of the mucosal muscular layer, and obstruction of the intestinal lumen.

　　Generally, there are no symptoms in clinical practice, abdominal colic may be an important sign, and in severe cases, it can cause partial intestinal obstruction. When intestinal stricture occurs in ulcerative colitis, one should be vigilant for tumors and differentiate between benign and malignant ones. Obvious colonic stricture can also occasionally be caused by colonic spasm, and the narrowing disappears after intravenous injection of glucagon. Endoscopic examination sometimes makes it difficult to exclude deep invasive cancer solely based on biopsy and cytological examination. If there is any suspicion of colon cancer, one should consider the possibility of colectomy. If the tumor can be ruled out, stricture can be eliminated by water balloon dilation without surgery; if not, surgical resection is required. Sometimes, in the stricture during the inflammatory activity stage, it can be caused by intestinal spasm, which diminishes with the control of inflammation.

　　Seven, Rectal and Perianal Lesions

　　Local complications of ulcerative colitis include hemorrhoids, anal fissures, perianal or ischiorectal abscesses, rectovaginal fistulas, and rectal prolapse. These complications are most likely to occur in patients with severe diarrhea. Anal fissures can improve when the colitis is controlled. Perianal abscesses and rectal fistulas can only heal after incision and drainage of the abscess or fenestration of the fistula. Hemorrhoids occur in 10% of patients, and rectal prolapse is often accompanied by cases of ulcerative colitis with long-term diarrhea during the active phase. More patients have pancolitis, which is related to the severity of diarrhea. Perianal lesions are seen in about 20% of patients, such as anal fistulas and perianal abscesses, which are far less common than in Crohn's disease. Abscesses often require conservative surgical treatment, such as drainage, and in severe cases, sometimes total colectomy may be necessary.

　　Systemic complications of ulcerative colitis with arthritic lesions:

　　One, Liver Lesions

　　15% of ulcerative colitis patients have varying degrees of liver function abnormalities, but only 2% to 5% have lesions. Pericholangitis accounts for 50% to 70% of liver and biliary tract lesions, which is actually a lymphocytic inflammation in the portal area. Most patients have normal liver function, but during biopsy, pericholangitis is shown, which can lead to recurrent bile stasis. Some patients may present with ascending cholangitis. Primary sclerosing cholangitis (PSC) is caused by inflammatory fibrosis and sclerotic damage to bile ducts inside and outside the liver, leading to bile duct obstruction and recurrent inflammatory attacks, presenting with cholestatic jaundice, itching, upper abdominal pain, and enlarged liver and spleen. About 10% of ulcerative colitis patients are complicated with PSC, and 50% to 70% of PSC patients have inflammatory bowel disease. Some patients have PSC before being diagnosed with inflammatory bowel disease, which increases the difficulty of diagnosis. The branch-like bile ducts can be confirmed by ERCP. The use of corticosteroids can suppress inflammation, and the use of antibiotics can treat retrograde infection. A few patients may develop biliary cirrhosis and bile duct cancer.

　　Two, Arthritis

　　The incidence of ulcerative colitis complicated with arthritis is about 11.5%, characterized by the occurrence of arthritis during the severe stage of colitis. Large joints are commonly involved, and it often presents as a single joint lesion. There is joint swelling and synovial effusion, but no damage to the bones and joints. There are no serological changes indicative of rheumatoid disease, and it often coexists with specific ocular and skin complications.

　　Three, Skin Lesions

　　Erythema nodosum is more common in the acute phase of colitis, with an incidence of 4.7% to 6.2%. It can be accompanied by arthritis, which is more common in women. Necrotizing pyoderma gangrenosum has not been reported in China. Chronic ulcers of the oral mucosa are also not uncommon, sometimes presenting as thrush, with poor treatment outcomes.

　　Four, Ophthalmopathy

　　Including iriditis, iridocyclitis, uveitis, corneal ulcer, etc. The former is the most common, seen in 5% to 10% of patients, more common in ulcerative colitis than in Crohn's disease. It is often accompanied by severe colitis, arthritis, skin lesions, aphthous ulcers in the mouth, etc., and also disappears with the control of colitis. Iriditis can threaten the patient's vision.

　　Five, Thromboembolic Complications

　　About 5% of cases, can occur in the abdomen, lungs, brain, and other parts of the body, or manifest as migratory thrombophlebitis, more common in women, and often related to the activity of the disease. It may be due to a hypercoagulable state formed by ulcerative colitis, with an increase in platelets and factors II, V, VIII, etc., which can disappear spontaneously after colectomy. Severe cases may be complicated by DIC. Vasculitis can also lead to ischemic infarction in multiple organs. In addition, ulcerative colitis can appear with a hypercoagulable state, with thrombosis and thromboembolism, and can also have thrombocytosis and arteritis.

　　Six, Growth Retardation

　　About 15% or more of ulcerative colitis patients. Patients are short and thin, and adolescents lack secondary sexual characteristics, mainly related to malnutrition and disease consumption.

　　Seven, Enteritis

　　The lesions complicated with enteritis are mainly located in the distal ileum, manifested as periumbilical or right lower quadrant pain, watery stools, and fatty stools, which accelerate the progression of systemic failure in patients.

　　Eight, Complications Caused by Drug Treatment Itself

　　For example, azathioprine and mercaptopurine can suppress bone marrow, causing thrombocytopenia, and occasionally can cause drug-induced pancreatitis; sulphasalazine can be complicated by acute pancreatitis; corticosteroids can be complicated by sepsis, peptic ulcer, diabetes, and cataracts, etc., which should also be paid attention to.

　　The male-to-female incidence ratio is 1.4:1 to 2.3:1, and the disease can occur in all age groups, with the most common age group being 20 to 50 years old. Generally, the onset is gradual, and a few patients may have an acute onset. The severity of the disease varies, and there is a tendency for recurrence. The factors for onset include emotional excitement, spiritual trauma, overexertion, dietary disorders, and upper respiratory tract infections. Systemic symptoms include anorexia, weight loss, normal or elevated body temperature, and during the acute phase, fever, tachycardia, and dehydration. The following are specific manifestations:

　　First, Gastrointestinal Manifestations

　　The most common abdominal manifestations of ulcerative colitis are diarrhea and intestinal bleeding, diarrhea is almost always present, while fever and weight loss are rare. The mucosal involvement of ulcerative colitis is extensive and continuous, including superficial ulcers, edema, friability, and small abscesses, which are localized to the colonic mucosa. Although Crohn's disease primarily involves the terminal ileum and colon, the lesions can be seen throughout the gastrointestinal tract. These lesions are often ulcerative and distributed in small patches. These lesions can be superficial, but are often transmural and granulomatous, with aphthous ulcers, pseudopyloric metaplasia, and sarcoma-like granulomas having diagnostic value. Ulcerative colitis and Crohn's disease can sometimes be difficult to distinguish from each other; when the lesions are localized to the colon, the histological findings will be helpful for differential diagnosis.

　　Two, Skin and Mucosal Manifestations

　　Common skin lesions include maculopapules, purpura, erythema multiforme, aphthous ulcers, erythema nodosum, and necrotizing pyoderma. Skin lesions often disappear with the resolution of intestinal inflammation. Aphthous ulcers and erythema nodosum usually appear within 24 hours after the acute onset of intestinal symptoms, and erythema multiforme often occurs after the appearance of intestinal symptoms. Necrotizing pyoderma is a recurrent skin ulcer that is easily allergic to iodine and bromine. Once allergic reactions occur, the skin lesions may worsen or spread to the whole body. It is usually distributed in the lower limbs and lower body. The onset is generally characterized by the appearance of one or more pustules, which then form and fuse into larger ulcers. Sometimes, red nodules may appear first, followed by the development of ulcers. The ulcers of necrotizing pyoderma are usually multiple and may be systemic.

　　Three, Articular Lesion Manifestations

　　In a study of 79 patients with active ulcerative colitis, 49 (62%) had joint involvement, with arthritis being oligoarticular and mostly asymmetric. It often presents as transient and migratory, affecting both large and small joints, primarily involving the lower limb joints. It is usually non-destructive and often resolves within 6 weeks, but recurrence is common. It may present with腊肠指(趾), tenosynovitis, particularly at the insertion points of the Achilles tendon or plantar fascia, and may also involve the knee or other sites. Crohn's disease may present with clubbing, while periostitis is rare. Some cases may develop chronic peripheral arthritis, and destructive damage to small joints and hip joints has been reported.

　　Four, Other

　　Ocular manifestations may include conjunctivitis, iridocyclitis, and uveitis, while the liver may present with fatty liver, pericholangitis, chronic active hepatitis, necrotizing cirrhosis, and sclerosing cholangitis. The kidneys may be affected by pyelonephritis, kidney stones, and glomerulonephritis. Other conditions may include iron deficiency anemia, autoimmune hemolytic anemia, microangiopathic hemolytic anemia, and thromboembolism. This disease may also overlap with Sjögren's syndrome, systemic sclerosis, polyarteritis nodosa, rheumatoid arthritis, mixed connective tissue disease, systemic lupus erythematosus, and other diseases. Once overlapping with other rheumatic diseases, the condition may quickly worsen. Additionally, the disease may also overlap with other autoimmune diseases such as multiple sclerosis, idiopathic biliary cirrhosis, idiopathic Addison's disease, and autoimmune diabetes.

　　Five, Extraintestinal and Articular Characteristics

　　Inflammatory bowel disease can present with various skin, mucosal, serosal, and ocular manifestations, with skin lesions being the most common, accounting for 10% to 25%. Erythema nodosum is often parallel to the activity of intestinal disease and is more likely to occur in patients with active peripheral arthritis, possibly indicating a disease-related manifestation. Necrotizing pyoderma is a more severe but less common extraintestinal manifestation that is not related to intestinal or joint diseases and may be a concurrent disease. It may also be associated with leg ulcers and thrombophlebitis.

　　Six, elderly ulcerative colitis

　　The most common clinical symptoms are bloody stools and bloody diarrhea. Zimmerman et al. reported that patients over 51 years old have more frequent diarrhea than those aged 21 to 30, with a longer duration of clinical symptoms. Most scholars believe that the main clinical manifestations and course of elderly ulcerative colitis are similar to those of young people. Zimmerman believes that the incidence of fulminant elderly-onset ulcerative colitis is higher, but this includes some recurrent cases that occurred before the age of 60 and those with delayed diagnosis leading to delayed treatment. Evans and Acheson found that the clinical manifestations of the disease are similar in the elderly and young, but elderly ulcerative colitis can have a more sudden onset tendency than young people. In a hospital with 29 elderly patients with ulcerative colitis, 13 were moderate to severe, significantly higher than the proportion of moderate to severe patients in young people. The other differences are that the most common clinical symptom in the elderly is diarrhea, while the common symptom in young people is intestinal bleeding. The reason for this difference in clinical manifestations is still unclear, but it suggests that attention should be paid to the possibility of ulcerative colitis in elderly patients with long-term recurrent diarrhea without blood in the stool, and an increased awareness of the disease can avoid misdiagnosis and mismanagement. In addition, compared with young people, elderly patients have a lower recurrence rate of the disease and extraintestinal complications, such as erythema nodosum, arthritis, uveitis, necrotizing pyoderma gangrenosum, and digital clubbing are very rare systemic complications.

　　Seven, pediatric ulcerative colitis

　　Clinical characteristics include mucous blood stools, and severe lower abdominal pain during defecation. According to the frequency of bowel movements, abdominal pain, fever, hemoglobin, and albumin levels, the clinical classification includes mild, moderate, and severe types. Mild cases have a slow onset, no obvious diarrhea, and generally have 3 to 5 bowel movements a day, with loose stools mixed with mucus and blood. When progressing to moderate to severe cases, the frequency can increase to 10 to 30 times a day, with obvious bloody diarrhea or mucous blood stools accompanied by urgency. Mir-Madjltssi reported that the incidence of pancolitis in pediatric patients is high, and sometimes the lesion may extend to the distal end. The risk of colectomy is greater in adult patients. This type is more common in infants and young children, and abdominal pain is often located in the lower left abdomen or lower abdomen. Severe children often have abdominal muscle tension and marked abdominal distension. Sometimes, the sigmoid colon or descending colon can be palpated for muscle spasm or thickening of the intestinal wall. Recently, Gry-bosky reported that in a group of 38 ulcerative colitis patients under the age of 10, although 71% of them had pancolitis (diagnosed by endoscopy or X-ray), most of the clinical cases were mild (53%) or moderate (37%). In an average follow-up of 6 to 7 years, only 2 cases underwent colectomy. With the improvement of medical methods, the support of parenteral nutrition, the application of broad-spectrum antibiotics and immunosuppressants, people are gradually using colonoscopy to monitor recurrence instead of prophylactic colectomy, which has led to a decrease in the number of children undergoing colectomy in recent years.

　　Prevention methods for ulcerative colitis arthritis:

　　Eliminate and reduce or avoid the factors causing disease, improve the living environment and space, develop good living habits, prevent infection, pay attention to dietary hygiene, and make reasonable dietary arrangements.

　　Secondly, pay attention to physical exercise, increase the body's ability to resist diseases, do not overwork, over-consume, quit smoking and drinking.

　　Early detection, early diagnosis, and early treatment, establish confidence in overcoming the disease, and persist in treatment.

　　The clinical examination of ulcerative colitis associated arthritis includes the following methods:

　　1. Blood routine and erythrocyte sedimentation rate

　　Anemia is low hemoglobin, small cell anemia. During the active stage of the disease, neutrophils increase, and erythrocyte sedimentation rate accelerates.

　　2. Routine fecal examination

　　Feces contain blood, pus, and mucus; fecal culture and hatchery, without Shigella, tissue-necrotizing ameba, schistosome eggs, and larvae, etc., specific pathogens of colitis.

　　3. Biochemical examination

　　Due to the increased activity of factor VIII, the generation of thrombin activator is accelerated, which can lead to hypercoagulability, with a significant increase in platelet count. In severe cases, serum albumin can decrease, and α1 and α2 globulins can increase significantly. During the remission period, the increase of α2 globulin is often a signal of recurrence. When γ-globulin decreases during the onset of the disease, it often indicates a poor prognosis. Severe patients can have significant electrolyte disorders, and hypokalemia can occur.

　　4. Immunological examination

　　Rheumatoid factor is negative, but when it overlaps with other rheumatic diseases such as rheumatoid arthritis, rheumatoid factor, LE cells, antinuclear antibodies, or other autoantibodies can be positive; IgG can be normal or decreased; IgA can increase or decrease; about half of the patients have a decrease in the number of E-rosette formation, a decrease in the PHA test, and a positive HLA-B27.

　　5. Laboratory examination of pediatric ulcerative colitis

　　Including routine fecal examination and culture as well as complete blood count. During the active stage of pediatric ulcerative colitis, blood sedimentation can accelerate, white blood cell count can increase, serum albumin can decrease, globulin can increase significantly, γ-globulin can decrease, immunoglobulin IgE can decrease, the number of T cells and T cell subsets can decrease, indicating the presence of immune complexes in the lesion site of the child. In the acute stage, acute phase reactants (erythrocyte sedimentation rate, C-reactive protein, serum rheumatoid factor level) are increased in 90% of Crohn's disease children, but they are relatively rare in ulcerative colitis. During the active stage of inflammatory bowel disease, polymorphonuclear neutrophils can accumulate in the segmental region of inflammation.

　　6. Barium enema X-ray examination

　　The colon pouches of the involved segment show shallow, disappearance, smooth or rough edges, most shallow small ulcers can make the colon edge appear with many fine hair-like protuberances, larger ulcers can cause a series of similar-sized ulcers on the colon edge, resembling the bottom of a push-button, but they are less common, and mucosal arrangement disorder, uneven thickness or unclear, can also appear deeper ulcers, which have a small ring of clear mucosal edema around them, with fine dot-like barium retention in the center, indicating the ulcerous cavity. The double-contrast imaging makes the ulcer more clear, most small ulcers can make the colon edge lose the normal smooth fine line state, and appear rough and uneven, as if a layer of fine crepe paper, the fine protuberant parts are the shadow of the ulcer, and larger ulcers can present a row of non-transparent small diverticulum-like protrusions outside the intestinal lumen, viewed from the front, they appear as high-density round plate-like, with a thin ring of clear edema around the barium.

　　7. Sigmoidoscopy

　　During the acute phase, the mucosa shows diffuse congestion, edema, hemorrhage, erosion, and is granular in appearance. There are numerous ulcers of irregular shape and depth, covered with yellowish or bloody exudates. In advanced patients, there may be thickening of the intestinal wall, stricture of the intestinal lumen, formation of pseudopolyps, and biopsy shows non-specific inflammatory changes and fibrous scars. At the same time, erosion, crypt abscesses, abnormal gland arrangement, and epithelial changes can also be seen.

　　8. Colonoscopy and X-ray examination for pediatric ulcerative colitis

　　9. Examination for pregnant patients with ulcerative colitis

　　General diagnostic measures for ulcerative colitis are applicable to pregnant patients, but X-ray examinations should be minimized. If it is necessary to perform a sigmoidoscopy to formulate a treatment plan during pregnancy, it should be ensured that the procedure is safely carried out. Total colonoscopy is contraindicated, and rectaloscopy should only be considered when necessary, especially in the first trimester of pregnancy.

　　Patients with ulcerative colitis arthritis should eat foods that clear heat and detoxify, are rich in high-quality protein, and enhance human immunity. They should avoid eating foods that irritate the gastrointestinal mucosa, such as chili, raw garlic, and ginger; avoid eating foods that are difficult to digest, such as rice cakes, rice noodles, and zongzi; and avoid eating foods that produce gas easily, such as potatoes, taros, and soybeans.

　　Common drugs and treatment methods for ulcerative colitis arthritis:

　　1. Common drugs:

　　1. Sulfasalazine class:Sulfasalazine has been used to treat ulcerative colitis for many years, taken orally at a dose of 4-6g/d, with efficacy in 64%-77% of patients. After symptom relief, the maintenance dose is 2g/d, for at least 1 year, with 89% of patients able to maintain asymptomatic status. Sulfasalazine is cleaved into mesalazine (5-aminosalicylic acid) and sulfapyridine by the azoreductase of intestinal bacteria in the colon. The former is the effective part for treatment, while the latter is the main factor causing side effects. If only mesalazine is taken, due to its absorption in the upper gastrointestinal tract, not enough medication reaches the colon, making it difficult to produce efficacy. In recent years, new oral formulations of mesalazine have been developed, such as Pentasa, Ascol, Olsalazine, Poly-mesalazine, and Balsalazide, which have reduced side effects due to the absence of sulfapyridine. In recent years, many scholars have noted that local administration can reduce side effects, such as the use of sulfasalazine or mesalazine enema or suppositories, which increases local drug concentration and maintains it for a longer time, thereby improving efficacy. There are also reports that local medication and systemic treatment have a synergistic effect, which can reduce the oral dose of sulfasalazine. Its therapeutic mechanism includes inhibiting the production of leukotrienes, prostaglandins, and other substances, as well as inhibiting the reaction of oxygen free radicals, but it can also cause skin rash, granulocytopenia, liver and kidney damage, and pancreatitis, with an incidence rate that is positively correlated with the dose.

　　2. 4-Aminosalicylic acid (4-ASA):Also known as PAS, it is an anti-tuberculosis drug, dissolved in 100ml of water at a dose of 2g, and administered by retention enema once a day for 8 weeks, with an efficacy rate of 83%. Ginsberg et al. reported that 4-ASA, taken orally in divided doses of 4g per day, after 12 weeks of treatment, 55% of patients had good efficacy. The mechanism of 4-ASA in the treatment of ulcerative colitis is still unclear.

　　3. Adrenal cortical hormones:It can reduce capillary permeability, stabilize cell and lysosome membranes, regulate immune function, reduce the entry of macrophages and neutrophils into the inflammatory area, block the formation of leukotrienes, prostaglandins, thromboxanes, etc., reduce inflammatory response, and quickly improve the clinical symptoms of ulcerative colitis. Generally, for active ulcerative colitis, prednisone (Prednisone) is taken orally at a dose of 40 to 60mg per day; for patients with severe illness and poor oral efficacy, intravenous infusion of hydrocortisone succinate at a dose of 200 to 300mg per day, or 100mg of hydrocortisone succinate added to 100ml of liquid for rectal infusion, is superior to retention enema.

　　Long-term use of glucocorticoids is prone to side effects, therefore, after the symptoms improve, the dosage should be gradually reduced, and the drug should be discontinued after 2 to 3 months. The remission rate of ulcerative colitis is 55.7% to 88.2%. Long-term continuous use of glucocorticoids for maintenance therapy cannot prevent recurrence. In recent years, some new types of corticosteroids such as Budesonide (Butidexin) and Thiocortopivalate, etc., have no systemic side effects. Enema treatment for ulcerative colitis is more effective than other corticosteroids. Fluticasone propionate is a flutocortosteroid with low systemic bioavailability after oral administration, which is not easily absorbed and most of it reaches the colon. It is taken orally at a dose of 5mg, 4 times a day, for a total of 4 weeks. Its efficacy is slightly lower than prednisone due to the small dose, but it can be improved by increasing the dose, although side effects are rare. There is also a glucocorticoid foam (Foam), which is administered rectally at a low dose with the same efficacy as high-dose hydrocortisone retention enema, and is more convenient than enema.

　　4. Immunosuppressants and immunomodulators:When the treatment with corticosteroids is not effective or cannot tolerate its side effects, azathioprine, cyclophosphamide, mercaptopurine, and other drugs can be selected; in recent years, methotrexate (methotrexate), cyclosporin-A (Cyclosporin-A) 10mg/kg have been applied, and sometimes good efficacy can be achieved, but these drugs all have certain side effects and should be used with caution. There are also reports that the use of penicillamine, levamisole, interferon, 7S-gamma globulin, and other drugs has certain efficacy.

　　5. Fish oil (Fishoil):It is a leukotriene synthesis inhibitor. Oral fish oil can assist in the treatment of mild to moderate active ulcerative colitis, and clinical improvement can be achieved. It has been reported that when treating with corticosteroids and sulfasalazine, the efficacy can be improved by taking oral fish oil 5.4g/d.

　　6. Metronidazole (Metronidazole):Can inhibit intestinal anaerobic bacteria and alleviate the symptoms of ulcerative colitis. In addition, metronidazole has an effect on the chemotaxis of white blood cells and certain immunosuppressive effects, which is effective for ulcerative colitis. However, due to large dosage and long-term use, gastrointestinal reactions are easy to occur.

　　7. Cromolyn:Can stabilize the membrane of mast cells, prevent degranulation, inhibit the release of histamine, 5-hydroxytryptamine, slow-reacting substances, and other mediators, and alleviate the damage to the intestinal wall caused by antigen-antibody reactions. 200mg per time, taken 3 times a day before meals; or 600mg enema, reported to have similar efficacy to prednisone 20mg.

　　8. Antimicrobial agents:For patients with concurrent infections, targeted antibiotics should be selected, but they should not be used as routine medication to avoid altering the efficacy and response of patients to sulfasalazine.

　　9. Other drugs:Clonidine (C可乐定) has the effect of inhibiting the release of renin and some neurotransmitters, with an oral dose of 0.15 to 0.225mg per time, 3 times a day, which is effective for ulcerative colitis. Calcium channel blockers such as verapamil (Isoprinal), nifedipine (Nifedipine), have the effects of antidiarrheal, analgesic, and inhibiting secretion. Quinapril 50mg, taken orally 4 times a day, also has good efficacy. Cimetidine (Cimetidine), ranitidine, and other H2 receptor blockers inhibit the release of histamine by intestinal mast cells, reducing the frequency of stools and other symptoms of ulcerative colitis. Chloroquine may slow down antigen response, promote normal function of intestinal epithelial cells, and alleviate the symptoms of ulcerative colitis. In addition, free radical scavengers such as Augmentin (superoxide dismutase), 5-lipoxygenase inhibitors Zileuton (A-64077), Ketotifen, can all alleviate the symptoms of ulcerative colitis.

　　2. Treatment of severe ulcerative colitis

　　1. Selection and application of corticosteroid hormones:For patients with severe left-sided colitis or extensive colitis lesions, hormone treatment is indispensable, and most of these patients require hospitalization.

　　(1) Management for patients who have not used oral corticosteroid hormones: Oral prednisolone (prednisolone) 40 to 60mg/d can be taken, and observed for 7 to 10 days, or it can be administered intravenously directly. Intravenous infusion of ACTH (120U/d) is more effective than hydrocortisone, prednisolone, methylprednisolone (methylprednisolone), dexamethasone, and other drugs, and symptoms can be significantly improved within 48 hours. Once the symptoms are controlled, the dose of hormones can be gradually reduced, and it is best to perform rectoscopy to monitor the activity of the lesion to guide hormone therapy. If symptoms do not relieve within 7 to 10 days, treatment with cyclosporin or surgical treatment should be selected based on the condition.

　　(2) Treatment for patients with poor efficacy after taking oral corticosteroid hormones: Intravenous hormone therapy is the first choice, and hydrocortisone 300mg/d (100mg, 3 times/d) or methylprednisolone 48mg/d (16mg, 3 times/d), prednisolone 30mg, twice daily, can be chosen. Increasing the dose does not increase efficacy, and symptoms usually improve within 48 hours. Once the symptoms are controlled, the dose of hormones can be gradually reduced, but the activity of the lesion should be monitored to guide hormone therapy. The combination of mesalazine may not be more effective, but the combination of mesalazine or hydrocortisone enema may help improve anal symptoms.

　　(3) Prognostic indicators of efficacy: A recent study has re-evaluated some indicators used to predict the efficacy of intravenous glucocorticoid treatment for severe colitis after 3 days. The results show that among these patients with severe ulcerative colitis, up to 85% of patients may require colectomy. The predictive indicators are more than 8 diarrhea episodes within 24 hours, or 4 to 5 diarrhea episodes within 24 hours, but C-reactive protein > 45mg/L. Based on these indicators, decisions can be made to administer intravenous cyclosporin or to undergo colectomy.

　　(4) Outcome: Patients who do not improve with the above treatment and are suspected to have perforation should undergo colectomy within 72 hours, as the mortality rate of perforation can reach 50%. For those with disappearing toxic symptoms, stopped bleeding, and alleviated abdominal pain and diarrhea, who can gradually start eating, prednisone (same as intravenous injection dose) can be taken orally, and the dose should be gradually reduced for patients with stable conditions. For those with disappeared toxic symptoms but persistent watery or bloody stools, consider extending treatment for 1 to 2 weeks, but not more than 2 weeks. If there is still no improvement, timely colectomy should be performed. There are reports that hormone treatment for 7 to 10 hours has not improved, and surgical treatment or the use of immunomodulatory agent cyclosporine can induce remission in 1/3 to 2/3 of patients, avoiding colectomy for at least half a year.

　　(5) Application of cyclosporin: For patients who are ineffective after 7 to 10 days of intravenous corticosteroid use, consider cyclosporin infusion of 2 to 4mg/kg per day. Due to the immunosuppressive effects of the drug, renal toxicity, and other adverse reactions, blood drug concentration should be strictly monitored. Therefore, considering the monitoring conditions of the hospital, it is advocated to use it in a few medical centers, and it is necessary to consider the effectiveness of surgical treatment and its excellent results when deciding whether to extend medical treatment.

　　It is now considered that cyclosporin infusion can be used as a transitional measure before surgery. Abroad, cyclosporin infusion of 4mg/kg has been used, with 59.8% (39/67) achieving remission, thus avoiding surgery in patients in extremely critical condition; however, 6 cases recurred after discontinuation of medication, and surgery was eventually performed; another 28 cases underwent colectomy. The overall short-term effective rate is 44%. Currently, it is popular to use cyclosporin to induce remission, followed by maintenance treatment with an immunosuppressant such as azathioprine. Through this therapy, more than half of the patients can avoid colectomy in the long term. Even in the short term, avoiding colectomy is beneficial to some patients, giving them time to consider whether to choose surgical treatment or other non-emergency treatment options.

　　2. Application of heparin类药物:Treating with heparin through intravenous or subcutaneous injection can significantly improve the patient's clinical condition. Due to the hypercoagulable state of the blood in ulcerative colitis patients, the incidence of thrombosis is significantly increased. We use nebulized inhalation of heparin to avoid the inconvenience of long-term injection, and heparin enters the lung and is taken up by endothelial cells, gradually released, which can extend the drug t1/2 and maintain a sustained effective blood concentration, safe, convenient, and effective. Due to the anticoagulant, antithrombotic, and anti-inflammatory effects of heparin, hematochezia is often the first symptom to be relieved.

　　Strictly select the indications for heparin类药物. The following situations may be tried: (1) Active ulcerative colitis patients with significant hypercoagulable states detected (e.g., platelets); (2) Patients with refractory ulcerative colitis dependent on or resistant to corticosteroids; (3) Early DIC.

　　3. Application of antibiotics:Adding antibiotics while using intravenous hormones has no therapeutic value, but it is recommended to use broad-spectrum antibiotics, such as third-generation cephalosporin antibiotics plus metronidazole, for those with peritoneal irritation signs, high fever, and increased white blood cells. The direct effect of antibiotics in the treatment of severe ulcerative colitis is unclear, but they can help improve symptoms in some cases.

　　4. Nutritional support and symptomatic treatment:

　　(1) Monitor vital signs: closely monitor the patient's vital signs and abdominal signs for changes, and detect and treat complications early.

　　(2) Bed rest, appropriate intravenous fluid therapy, and electrolyte supplementation to prevent water and electrolyte imbalance.

　　(3) For patients with large amounts of fecal blood, hemoglobin (Hb) below 90g/L, and persistent bleeding, blood transfusion should be considered.

　　(4) For patients with malnutrition and severe illness, elemental diet can be used, and total parenteral nutrition (TPN) should be given for severe illness.

　　Parenteral nutrition has no direct therapeutic effect on ulcerative colitis, but it is beneficial for maintaining complete intestinal rest, improving nutrition, and correcting water and electrolyte imbalances. If tolerated, early recovery of渣-free diet is also very important. Currently, it is generally倾向于，for severe colitis patients, complete parenteral nutrition therapy is given routinely. There are also some comparative study results that have not proven the benefits of TPN, even some believe that due to the TPN therapy, it may stop the supply of short-chain fatty acids necessary for the metabolism and repair of intestinal cells in the colon. However, when severe ulcerative colitis patients have serious nutritional deficiencies, TPN as an auxiliary nutritional treatment is still necessary.

　　(5) Symptomatic treatment: Patients with megacolon should undergo nasogastric tube gastrointestinal decompression, and the anal canal also has a decompressive effect. Changing positions helps to expel colonic gas. Laxatives, sedatives, and anticholinergic drugs may induce megacolon or intestinal obstruction, and should be avoided.

　　(6) Surgical treatment: If the efficacy of drug treatment is poor as mentioned above, or if there is toxic megacolon, it is necessary to consult with internal medicine and surgery in a timely manner to determine the timing and method of colon resection surgery.

　　In summary, although the treatment of severe ulcerative colitis is a clinical challenge, most patients can achieve remission by taking different measures according to different situations.

　　3. Treatment of distal ulcerative colitis

　　The disease involves the distal 30-40cm of the colon and is called distal ulcerative colitis, also known as sigmoid colonitis. There is often bloody stool, and mild to moderate patients generally have no systemic symptoms or only mild symptoms. Treatment for mild to moderate distal colitis: For patients with proctitis or distal colitis, oral or local treatment methods are generally effective, and the treatment plan depends to some extent on the patient's own choice (such as whether willing to take oral medication, whether able to adapt to local administration, or how the economic bearing is, etc.).

　　1. Aminosalicylic acid drugs: Common mesalazine preparations include:

　　Local agent: Mesalazine enema or local irrigation, the method is simple and practical. Due to the high concentration of local drugs and their long-term maintenance, the efficacy is significantly improved, while systemic adverse reactions are reduced. Mesalazine enema treatment for ulcerative colitis and comparison with sulfadiazine and sulfapyrazine. The results showed that 75% of patients with mesalazine or sulfapyrazine enema had clinical and sigmoidoscopy improvement, while the response rate in the sulfadiazine group was only 35%. We treated 10 patients with mild to moderate left-sided ulcerative colitis with 4g of mesalazine enema, with a clinical and colonoscopy improvement rate of 90%, and a histological remission rate of 80%. Its efficacy is higher than that of hydrocortisone. The drugs for enema are generally only absorbed by 20% in the colon, acetylated and excreted in the urine. The dose of rectal medication is small (500mg), which can be taken 2-3 times a day, and is usually effective for ulcerative proctitis.

　　2, Adrenal cortical hormones:Patients who are still ineffective after 4 to 6 weeks of treatment with aminosalicylate drugs, or who are intolerant or allergic to mesalazine, should be treated with adrenal cortical hormones, such as hydrocortisone (100mg/d) retention enema, do not exceed 3 weeks of medication per dose. There are already various new formulations of glucocorticoids on the market abroad, such as the rapidly metabolizing tixocortolpivalate enema solution, which is more effective than traditional corticosteroids and has few systemic adverse reactions. Budesonide (trade name Entocort, i.e., budesonide enema) retention enema can also be used. It has an extremely high first-pass effect, so it has almost no systemic effects. At a dose of 2mg, it can be equivalent to the effect of 20 to 30mg of prednisone (or 100mg of hydrocortisone). There are no adverse effects on the hypothalamic-pituitary-adrenal axis after repeated multiple courses of budesonide enema treatment. Therefore, long-term use of budesonide has good safety. The standard dose is 9mg, and increasing it to 15mg does not increase efficacy and has the effect of inhibiting adrenal cortex, resulting in a decrease in the morning plasma cortisol concentration. The dose of 18mg has more adverse reactions, but it is still lower than systemic medication. In addition, another locally applied adrenal cortical hormone foam preparation, namely the rectal hydrocortisone foam suppository, has also been used to treat this disease. Each rectal injection is 5ml, which is equivalent to the effect of 100mg of hydrocortisone enema, and it is more convenient than enema, does not affect the patient's daily life, and thus provides another treatment method for patients with this disease. Most of these drug treatments can quickly relieve the lesions, but recurrence is likely upon discontinuation. It is also feasible to treat severe symptoms with oral or intravenous corticosteroid drugs, and it is necessary to reduce the dose promptly once the symptoms are relieved.

　　Treatment of refractory distal colitis

　　If the distal active colitis of the patient is ineffective after 4 to 6 weeks of treatment with mesalazine or corticosteroid preparations applied locally, or with the combination of oral aminosalicylic acid or sulfasalazine preparations, then these patients should be classified as having 'refractory distal colitis' (refractory distal colitis). It is appropriate to extend the administration time for further treatment and observation or to switch to other medications for treatment. Some patients with proctitis that is ineffective to mesalazine may show efficacy to corticosteroid enema solutions, or may be ineffective to corticosteroid enema treatment but effective to mesalazine preparations. Another method worth considering is the combined use of mesalazine and corticosteroid hormones in enema. Mulder et al. reported that the combined enema of beclomethasone dipropionate (also known as beclomethasone dipropionate, beclomethasonedipropionate) 3mg and mesalazine 1g was effective for some refractory lesions.

　　1, whether to use cyclosporin (cyclosporin) enema is still controversial.The study results of enema treatment with nicotine tartrate solution show that after enema with a dose of nicotine base 3mg/d for 1 week, then enema with a dose of 6mg/d for 3 weeks, in patients with mild to moderate active left-sided ulcerative colitis who are ineffective to the first-line therapy, a part of them have achieved clinical improvement.

　　2, maintenance treatment:Patients with initial onset in China can discontinue medication after remission. For those with slow response to treatment, insensitive to conventional treatment, or recurrence within a few weeks after stopping treatment, maintenance treatment should be continued. Mesalazine suppository once a day at night is the most effective method for maintaining remission, and there are also those who maintain remission every other day or even every 3-4 days, with 54%-80% able to maintain remission for 1 year. However, due to the inconvenience of using enema for maintenance treatment, many patients prefer oral medication, which can also maintain remission. Sulfasalazine 4g/d is more effective than 2g/d, but low-dose can improve patient compliance and reduce side effects. Generally, azathioprine or 6-mercaptopurine is not used for maintenance treatment unless the patient is ineffective or dependent on corticosteroids.

　　3, surgical treatment:Surgical treatment is rarely used unless there are serious complications or suspected malignancy.

　　4, treatment for left hemicolitis and total colitis:When inflammation involves the splenic flexure of the colon, it is called left hemicolitis, and when it involves beyond the hepatic flexure, it is called total colitis. Because the extent of the lesion exceeds the reach of local therapy (such as the middle segment of the descending colon to the splenic flexure), oral medication or combined with local medication is generally required.

　　Five, treatment for mild to moderate patients

　　Aminosalicylic acid drugs: The traditional therapy is still oral administration of a large dose (4-6g/d) of sulfasalazine. About 80%