Amoebic colitis

　　1. Etiology

　　Entamoeba histolytica is the only pathogenic ameba in humans, existing in three forms: large trophozoites, small trophozoites, and cysts in human tissues and feces. Trophozoites have weak resistance to external factors outside the body and are prone to death, while cysts have strong resistance to the external environment:

　　1. Trophozoites The large trophozoites are 20 to 40 μm in size, moving in a certain direction by pseudopodia, found in the feces or intestinal wall tissues of acute patients, engulfing tissues and red blood cells, hence also known as tissue-type trophozoites; the small trophozoites are 6 to 20 μm in size, with fewer pseudopodia, feeding on the host's intestinal fluid, bacteria, and fungi, not engulfing red blood cells, also known as intestinal lumen-type trophozoites. When the host's resistance decreases, they secrete tissue-damaging enzymes, and with their own movement, they invade the submucosal layer of the intestinal mucosa, becoming large trophozoites; when the conditions in the intestinal lumen change and are unfavorable for their activity, they become pre-cystic forms, and then become cysts. Trophozoites have no significant role in transmission.

　　2. Cysts are commonly found in the feces of asymptomatic and chronic patients, appearing as round shapes with a size of 5 to 20 μm. Mature cysts have four nuclei and are the infective form of tissue-damaging Amoeba, being infectious. Cysts have strong resistance to external conditions, surviving at least 2 weeks in feces, 5 weeks in water, and 2 months in the refrigerator. They are also resistant to chemical disinfectants, capable of tolerating potassium permanganate at a concentration of 0.2% for several days. The chlorine concentration used for drinking water disinfection has no killing effect on them, but they are very sensitive to high temperatures (50℃) and dryness.

　　3. The pathogenicity of Amoeba is a complex process involving the interaction between the parasite and the host, influenced by various factors. The invasive power of the tissue-damaging Amoeba is mainly manifested in its ability to dissolve and destroy host tissues. It has been proven in the past that Amoeba has various proteolytic enzyme activities, but they have never been successfully isolated. In the early 1970s, experiments showed that the trophozoite's destructive effect on host cells has the characteristic of contact lysis, and enzymes capable of hydrolyzing gelatin, casein, fibrin, and hemoglobin were extracted from the living Amoeba. Experiments and electron microscopy observations indicate that trophozoites can not only engulf red blood cells but also kill white blood cells. Recent studies have shown that the virulence of Amoeba is hereditary, but the intensity of virulence varies with the strain. Due to the long-term adaptation of Amoeba strains in tropical regions to intracellular parasitism, they have a strong virulence and high incidence rate; while in cold and temperate regions, the virulence of the strains is weaker, and more carriers are found. The occurrence of virulence is related to the bacteria accompanying the intestinal lumen, having a synergistic effect on pathogenicity. It is likely that bacteria can provide the physical and chemical conditions for the proliferation and activity of Amoeba, and they may also weaken the host's systemic or local resistance, even directly damaging the intestinal mucosa, providing an opportunity for Amoeba to invade tissues. The culture of tissue-damaging Amoeba requires the presence of bacteria, showing a symbiotic phenomenon. Currently, symbiotic culture has been successfully achieved, providing conditions for the preparation of pure antigens and in-depth research on tissue-damaging Amoeba. In addition, the host's immune status plays an important role in whether Amoeba can invade tissues. Dysentery Amoeba must break through the host's defense barrier to invade tissues and reproduce. Clinical and experimental data indicate that factors such as malnutrition, infection, intestinal dysfunction, and mucosal injury that lead to low systemic or local immune function are favorable for Amoeba's invasion of tissues. In populations with low nutritional standards, the incidence of Amoeba is significantly higher than that of those with balanced diets, and it is not easily controlled by drugs; patients with intestinal or systemic infections such as typhoid, schistosomiasis, and tuberculosis are prone to Amoeba disease, and it is not easy to be cured after becoming ill.
4. After the amebic cyst enters the digestive tract, it is digested by trypsin and other digestive fluids in the lower segment of the small intestine, and the organism escapes from the cyst, repeatedly divides to form small trophozoites, and resides in hypoxic regions such as the ileocecal junction, colon, etc. In healthy hosts, the small trophozoites move downward with the feces and become cysts excreted out of the body, causing no disease. Under favorable conditions, such as when the gastrointestinal function of the body is reduced or local intestinal mucosal injury occurs, the trophozoites release lysosomal enzymes, hyaluronidase, and protease, and rely on the mechanical activity of their pseudopodia to invade the intestinal mucosa and submucosa, reproduce in large numbers, destroy the tissue, form small abscesses and creeping (cup-shaped) ulcers, causing extensive tissue destruction that can reach the muscular layer. The large trophozoites are excreted from the intestines with necrotic material and blood, presenting with dysentery-like symptoms. In chronic lesions, the mucosal epithelium proliferates, granulation tissue forms at the bottom of the ulcer, fibrous tissue proliferation and hypertrophy are seen around the ulcer, forming intestinal amoebiasis. In cases with a long course, it can lead to thickening of the intestinal wall and narrowing of the intestinal lumen. The intestinal trophozoites can also spread directly to surrounding tissues, forming various lesions such as rectovaginal fistula or skin and mucosal ulcers. In some cases, it can cause intestinal hemorrhage, intestinal perforation, or complications such as peritonitis and appendicitis.

　　2. Pathogenesis

　　The large trophozoites of Entamoeba histolytica invade the intestinal wall, causing amoebiasis. The common sites are the cecum, followed by the rectum, sigmoid colon, and appendix. The transverse colon and descending colon are less common, and sometimes the entire large intestine or part of the ileum may be involved. Under the microscope, the main lesion is tissue necrosis, with visible infiltration of lymphocytes and a small number of neutrophils. If bacterial infection is severe, it can present as acute diffuse inflammation with a large number of inflammatory cells infiltrating, mucosal edema, and necrosis. Multiple amebic trophozoites can be seen at the damaged site, mostly aggregated at the edge of the ulcer.

　　1. During the acute phase, the intestinal mucosa is damaged, leading to erosion and superficial ulcers. If the lesion continues to progress and involves the submucosal layer, it forms a typical bottle-like ulcer with a small mouth and a large base, filled with brownish-yellow necrotic material containing dissolved cell fragments, mucus, and trophozoites. The expulsion of the contents produces clinical dysentery-like stools. Unlike bacterial dysentery, the mucosa between the ulcers is mostly intact. Due to the loose tissue of the intestinal wall, the ameba continues to progress into the submucosal layer, the protozoa spreads laterally along the intestinal longitudinal axis, causing the dissolution of a large amount of tissue and forming many fistulae connected honeycomb-like areas. There is a lot of inflammatory reaction around the focus, generally only with the infiltration of lymphocytes and a few plasma cells. If there is secondary bacterial infection, there may be a large number of neutrophils infiltrating, and the lesion site is prone to form capillary thrombosis, petechial hemorrhage, and necrosis. Due to the destruction of small blood vessels, the excrement contains a large number of red blood cells. In severe cases, the lesions can reach deep into the serosal layer, even penetrate it. Since the lesion progresses gradually, the serosal layer is prone to adhesion with adjacent tissues, so acute intestinal perforation is not common. Amoebic ulcers are generally deeper and tend to erode blood vessels, causing massive intestinal hemorrhage. During the healing process of the lesion, the regression of tissue reaction can be seen, with the disappearance of lymphocyte infiltration and the replacement of connective tissue.

　　2. In the chronic stage, the characteristics are the hyperplasia of the intestinal mucosal epithelium, the appearance of granulation tissue at the bottom of the ulcer, fibrous tissue hyperplasia around the ulcer, and the coexistence of tissue destruction and healing, which thickens the intestinal wall and narrows the intestinal lumen. The connective tissue occasionally shows tumor-like proliferation, becoming an amoeboma, which is more common in the anal, anal-rectal junction, transverse colon, and cecum. Amoebomas may be very large, hard, and difficult to differentiate from colorectal cancer.

　　1. The incidence of amoebic intestinal perforation is 1% to 4%, and the incidence of intestinal perforation in amoebic autopsies is 3% to 20%. Acute perforation most often occurs in the cecum, appendix, ascending colon, followed by the rectum and the junction of the sigmoid colon, most often in patients with acute amoebic dysentery with acute symptoms. Perforation leads to diffuse peritonitis, with a dangerous condition. Early surgical treatment should be performed.

　　2. Amoebic appendicitis and appendiceal abscesses are more common due to the frequent occurrence of amoebic colitis in the cecum. In autopsies of cases with colonic amoebiasis, 4.0% to 6.2% were found to have amoebic appendicitis, and some formed abscesses or perforations. Pure amoebic appendicitis is rare. The symptoms are similar to those of bacterial appendicitis, and the lesion is often found to be not limited to the appendix during surgery, with the cecum wall showing thickening and edema. In this situation, it is not only difficult to deal with the appendiceal stump, but also it is easy to form an appendiceal stump fistula after surgery.

　　3. Amoebic granuloma lesions are commonly found in the cecum, followed by the sigmoid colon, descending colon, and rectum. 5% to 10% are multiple. In the early stage, there may be no symptoms, but as the condition progresses, symptoms such as localized abdominal pain, diarrhea, and fever may appear. The proliferative granulomas can cause intestinal stricture, leading to intestinal obstruction, intussusception, massive hemorrhage, intestinal wall perforation, or formation of internal and external fistulas by penetrating the abdominal wall. Palpation may reveal a hard mass in addition to local tenderness. Barium enema X-ray examination shows filling defects and intestinal stricture. Amoebic abscesses and granulomas in the intestinal wall project into the lumen, forming saw-toothed shadows. Sigmoidoscopy shows thickening of the mucosa, with the mass protruding into the lumen like grapes, and scattered granuloma tissue and ulcers are often present nearby. Biopsy specimens taken from the bottom of the ulcer for histological examination show a high detection rate of amoebic trophozoites. Amoebic granuloma is often misdiagnosed as intestinal tumor, and the diagnosis can only be confirmed by postoperative pathological examination of amoebae. After treatment of amoebiasis with medication, scarred stricture or internal and external fistulas may remain, and surgical treatment should be considered.

　　4. Chronic amebic enteritis in colon cancer or rectal cancer may coexist with colon cancer or rectal cancer. Some believe that it may be caused by chronic inflammation stimulating the intestines. Inflammatory polyps also facilitate carcinogenesis.

　　5. The amebic protozoa causing gastrointestinal bleeding extend along the longitudinal axis of the intestine, causing large amounts of tissue dissolution in the intestinal wall. The lesions can extend deep into the serosa layer. When large blood vessels are corroded, massive intestinal hemorrhage can occur. Patients may present with increased frequency of defecation, fresh blood in the stool, and in severe cases, weakness, tachycardia, and blood pressure drop.

　　First, acute amebic enteritis

　　1. Asymptomatic type: The majority of amebic colitis patients are of this type. Cysts can be found in the feces, but there are no symptoms. Occasionally, it can invade the intestinal mucosal tissue and cause lesions.

　　2. Common type: The onset is relatively slow, with generally mild toxic symptoms. Daily diarrhea occurs 1-4 times, with malodorous stools,呈稀便或暗红色果酱样, containing mucus and pus. Severe cases may have diarrhea tens of times a day with a sense of urgency to defecate, often accompanied by bloating and abdominal绞痛. Physical examination may reveal that patients of this type often have liver enlargement and abdominal tenderness.

　　3. Fulminant type: Seen in explosive outbreaks caused by waterborne transmission. This type is more common in the weak or those with low immune function. The onset is sudden, with high fever reaching 40-41°C, marked toxic symptoms, extreme exhaustion, abdominal pain, and the passage of large amounts of bloody diarrhea. It may be accompanied by a sense of urgency to defecate. It is prone to complications such as intestinal hemorrhage and perforation. The stool examination can show a large number of amebic trophozoites.

　　Second, chronic amebic enteritis

　　2. This type is often caused by incomplete treatment of the common type, and patients may experience alternating diarrhea and constipation with abdominal discomfort. Symptoms can persist or appear intermittently, with intermittent periods ranging from several weeks to several months or even years. Fatigue, catching a cold, and improper diet can trigger the disease, and recurrent attacks may lead to ulcerative colitis.

　　1. Recurrent intestinal disorders or dysentery-like diarrhea with unclear etiology, or when sulfonamide drugs and antibiotics are ineffective, amebic colitis should be considered. Pathological examination is an important diagnostic basis. The presence of amebic pathogens in feces can confirm the diagnosis. Usually, the presence of large trophozoites indicates an acute case, while the presence of small trophozoites or cysts indicates only infection.

　　1. Develop good living habits, quit smoking and limit alcohol intake. Smoking, according to the World Health Organization's prediction, if people stop smoking, cancer in the world will decrease by 1/3 after 5 years; secondly, do not drink excessively. Tobacco and alcohol are highly acidic substances, and people who smoke and drink for a long time are prone to acidic体质.

　　2. Avoid eating too much salty and spicy food, do not eat overcooked, cold, expired, or deteriorated food; the elderly, the weak, or those with certain genetic predispositions to diseases should eat some cancer-preventive foods and alkaline foods with high alkalinity in moderation, and maintain a good mental state.

　　First, Feces Examination

　　1. Live trophozoite examination method: The direct smear method with physiological saline is commonly used to check active trophozoites. The typical amebic dysentery feces is sauce-red mucus-like, with a special smell, and the examination of purulent stools in acute dysentery patients or loose stools in amebic patients can be observed under a microscope, showing a large number of aggregated red blood cells and a small number of white blood cells in the mucus, and sometimes active trophozoites can be seen. These characteristics can be distinguished from the feces of bacterial dysentery. When collecting specimens, the container should be clean, the feces fresh, and the sooner the inspection is sent, the better. In cold seasons, attention should also be paid to the warmth of transportation and examination.

　　2. Cyst examination method: The iodine solution smear method is commonly used in clinical practice, which is simple and easy to operate. Take a clean slide, add one drop of iodine solution, then use a bamboo stick to take a small amount of feces and spread it into a thin film in the iodine solution, cover with a cover slip, and then examine under a microscope to differentiate the characteristics and number of the nucleus of the cells.

　　Second, Amebic Culture

　　There are various improved artificial culture media, commonly used ones include洛克氏液洛克氏液, egg white, serum culture medium, nutrient agar serum salt culture medium, and agar proteinase double-phase culture medium, etc. However, the technical operation is complex, requires certain equipment, and amebic artificial culture has a low positive rate in most subacute or chronic cases, and is generally not suitable as a routine examination for amebic diagnosis.

　　Third, Immunodiagnosis

　　In recent years, various serological diagnostic methods have been reported in China and abroad, among which indirect hemagglutination (IHA), indirect fluorescent antibody (IFAT), and enzyme-linked immunosorbent assay (ELISA) have been studied more. However, the sensitivity varies for different types of cases. IHA has higher sensitivity, with a positive rate of 98% for intestinal amebiasis and 95% for extra-intestinal amebiasis, while asymptomatic carriers only have a 10% to 40% positive rate. IFAT has slightly lower sensitivity than IHA, EALSA has strong sensitivity and high specificity, with promising prospects. Other methods such as gel diffusion precipitation test, intradermal test, etc., all have the value of auxiliary diagnosis. In recent years, there have been reports of successful detection of amebic specific antigens in feces and pus using sensitive immunological techniques, especially the application of monoclonal antibodies against amebas, which provides a reliable, sensitive, and anti-interference method for detecting pathogenic substances in the host's excretions.

　　Fourth, Blood Examination

　　The total and differential counts of peripheral blood leukocytes are usually normal. In cases of fulminant or secondary bacterial infection, the total leukocyte count and the proportion of neutrophils may increase, and chronic patients may have mild anemia.

　　Fifth, Colonoscopy Examination

　　Most cases show scattered ulcers of varying sizes, with exudation at the center, regular edges, and sometimes a red halo around them. The mucosa between the ulcers is normal. Smears and biopsies from the edges of the ulcers show trophozoites. Direct observation of mucosal ulcers and tissue biopsy or scraping smear through sigmoidoscopy or colonoscopy has the highest detection rate. It is reported that about 2/3 of the cases with rectal or sigmoid colon lesions have symptoms, therefore, all suspicious patients whose conditions permit should strive for colonoscopy, scraping smear or tissue biopsy. The sampling of trophozoites must be from the edges of the ulcers, and it is preferable for there to be slight bleeding after clamping. The examination of pus cavity穿刺液 should be taken from the wall of the pus cavity, which is more likely to discover trophozoites.

　　6. Barium enema造影

　　It can be seen that there are defects in filling and the intestinal lumen is relatively narrow, amebic abscesses and granulomas in the intestinal wall protrude into the intestinal lumen, forming serrated shadows.

　　1. Diet should consist mainly of low-fiber, easily digestible foods, avoid spicy and strong-flavored seasonings. Pay attention to the cleaning of food, it should be cooked, and avoid secondary bacterial infection.

　　2. Strengthen physical exercise and advocate participation in jogging. Physical exercise can increase the oxygen supply to all tissues in the body, especially jogging, which can coordinate the participation of all parts of the body in exercise, increase vitality, and improve and restore normal physiological functions. For elderly and weak patients, jogging is not recommended, and moderate walking can be done instead.

　　1. The treatment principle of this disease is

　　Select effective drugs to cure amebiasis in the intestines; correct water and electrolyte imbalances; prevent complications, especially the occurrence of peritonitis.

　　1. General treatment includes strengthening physical fitness, alleviating symptoms, replenishing body fluids, and correcting electrolyte imbalances.

　　2. Pathogenic treatment: Pathogenic treatment usually requires the combined use of antiamoebic drugs for intracellular and intraluminal amebiasis. In severe epidemic areas, intermittent collective administration of metronidazole or dichloronitrazole (dichlorodifluoromethane) can be considered.

　　2. Antiamoebic drugs for intracellular amebiasis

　　Including metronidazole, tinidazole, dehydroemetine, and others. Metronidazole is the first choice, 1.0-1.2g per day, divided into 3 doses after meals, for 5-10 consecutive days; children 50mg/(kg·d), divided into 3 doses, for 7 consecutive days. The main side effects are gastrointestinal reactions, and women in early pregnancy and lactation should avoid using this drug. In addition, alcohol should not be consumed before or after taking this medication, otherwise, a disulfiram-like reaction may occur (flushing of the face, increased pulse rate, difficulty breathing, rash, vomiting, followed by pale complexion, low blood pressure, and in severe cases, arrhythmia, myocardial infarction, and other conditions). The dose of tinidazole for adults is 1-2g per day, and for children, 30-40mg/(kg·d), taken once a day in the morning, for 5 consecutive days. This drug has rapid absorption, a long half-life, and few side effects.

　　3. Antiamoebic drugs for intraluminal amebiasis

　　Tetracycline is effective against the trophozoites in the intestinal lumen and wall, with a dose of 500mg, 4 times a day, for 5 consecutive days. Halogenated hydroxyquinolones have good oral efficacy due to high concentration in the intestinal lumen, effective for those with mild symptoms and asymptomatic excretion of cysts. This class of drugs includes Quinoform, with a dose of 500mg, 3 times a day, for 10 consecutive days, and can be supplemented with 1% solution retention enema of 100-150ml; the dose of diiodohydroxyquinone is 600mg, 3 times a day, for 15-20 consecutive days. The main side effects of this class of drugs are diarrhea, occasionally nausea, vomiting, and abdominal discomfort. Patients with iodine allergy and those with thyroid disease should avoid using these drugs. Dichloronitrazole is a newly synthesized antiamoebic drug, with a dose of 500mg, 3 times a day, for 10 consecutive days.

　　2. For acute amoebic enteritis, metronidazole or emetine (ipecac alkaloid) should be used, plus broad-spectrum antibiotics (tetracycline); for chronic amoebic dysentery, metronidazole or tinidazole 1 or 2 courses should be used. If it has not been cured, other drugs acting on intestinal protozoa, such as chinioform, can be used for treatment.

　　IV. Symptomatic Treatment

　　For patients with high fever, antipyretics should be used; for those with respiratory failure, central respiratory stimulants such as nikethamide should be used, and at the same time, water and electrolyte imbalances should be corrected; in case of intestinal bleeding or shock, blood transfusion should be performed in a timely manner and vasoactive drugs should be added; when there is mixed bacterial infection, appropriate antibiotics should be used for treatment, etc.

　　V. Treatment of Complications

　　1. Treatment of intestinal perforation: Immediate surgical exploration should be performed when intestinal perforation occurs. Small perforations can be sutured and repaired, and abdominal drainage should be placed at the same time; if there are multiple perforations or large perforations, and the intestinal wall has large areas of necrosis, it is estimated that repair is difficult, local colon resection should be considered. If anastomosis is difficult, perform a two-end stoma or place the perforated intestinal segment externally, and perform a second-stage intestinal anastomosis surgery later. If the patient's condition is critical and it is difficult to remove or place the perforated intestinal segment, only a proximal intestinal endostomy or loop stoma can be performed, and a tube should be placed for drainage of the perforated necrotic area. Postoperative active treatment of amoebiasis and peritonitis is required. The prognosis of these patients after surgery is often poor, and the mortality rate is high.

　　2. Colonic amoebic granuloma: If drug treatment is ineffective, surgical treatment is required, which involves resecting the granuloma segment of the intestine and performing an intestinal anastomosis.

　　3. Amoebic appendicitis: It is difficult to diagnose before surgery, and it is usually found that in addition to appendiceal lesions, the cecum wall is thickened during surgery, and the possibility of colonic amoebiasis should be considered, and drug treatment is needed. If the residual end after appendectomy does not heal well, forms an abscess, or forms a fistula after drainage, the drain should be sent for pathological examination to find the amoeba protozoa for an accurate diagnosis, and drug treatment may help it heal.