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Stem cell therapy is undergoing research as a possible treatment for IBD. A review of studies suggests a promising role, although there are substantial challenges, including cost and characterization of effects, which limit the current use in clinical practice.
Medical treatment of IBD is individualised to each patient. The choice of which drugs to use and by which route to administer them (oral, rectal, injection, infusion) depends on factors including the type, distribution, and severity of the patient's disease, as well as other historical and biochemical prognostic factors, and patient preferences. For example, mesalazine is more useful in ulcerative colitis than in Crohn's disease. Generally, depending on the level of severity, IBD may require immunosuppression to control the symptoms, with drugs such as prednisone, TNF inhibitors, azathioprine (Imuran), methotrexate, or 6-mercaptopurine.
Steroids, such as the glucocorticoid prednisone, are frequently used to control disease flares and were once acceptable as a maintenance drug. Biological therapy for inflammatory bowel disease, especially the TNF inhibitors, are used in people with more severe or resistant Crohn's disease and sometimes in ulcerative colitis.
Treatment is usually started by administering drugs with high anti-inflammatory effects, such as prednisone. Once the inflammation is successfully controlled, another drug to keep the disease in remission, such as mesalazine in UC, is the main treatment. If further treatment is required, a combination of an immunosuppressive drug (such as azathioprine) with mesalazine (which may also have an anti-inflammatory effect) may be needed, depending on the patient. Controlled release Budesonide is used for mild ileal Crohn's disease.
Symptoms of short bowel syndrome are usually addressed with medication. These include:
- Anti-diarrheal medicine (e.g. loperamide, codeine)
- Vitamin, mineral supplements and L-glutamine powder mixed with water
- H2 blocker and proton pump inhibitors to reduce stomach acid
- Lactase supplement (to improve the bloating and diarrhoea associated with lactose intolerance)
In 2004, the USFDA approved a therapy that reduces the frequency and volume of total parenteral nutrition (TPN), comprising: NutreStore (oral solution of glutamine) and Zorbtive (growth hormone, of recombinant DNA origin, for injection) together with a specialized oral diet. In 2012, an advisory panel to the USFDA voted unanimously to approve for treatment of SBS the agent teduglutide, a glucagon-like peptide-2 analog developed by NPS Pharmaceuticals, who intend to market the agent in the United States under the brandname Gattex. Teduglutide had been previously approved for use in Europe and is marketed under the brand Revestive by Nycomed.
Surgical procedures to lengthen dilated bowel include the Bianchi procedure, where the bowel is cut in half and one end is sewn to the other, and a newer procedure called serial transverse enteroplasty (STEP), where the bowel is cut and stapled in a zigzag pattern. Heung Bae Kim, MD, and Tom Jaksic, MD, both of Children's Hospital Boston, devised the STEP procedure in the early 2000s. The procedure lengthens the bowel of children with SBS and may allow children to avoid the need for intestinal transplantation. As of June 2009, Kim and Jaksic have performed 18 STEP procedures. The Bianchi and STEP procedures are usually performed by pediatric surgeons at quaternary hospitals who specialize in small bowel surgery.
Mild cases usually do not require treatment and will go away after a few days in healthy people. In cases where symptoms persist or when it is more severe, specific treatments based on the initial cause may be required.
In cases where diarrhoea is present, replenishing fluids lost is recommended, and in cases with prolonged or severe diarrhoea which persists, intravenous rehydration therapy or antibiotics may be required. A simple oral rehydration therapy (ORS) can be made by dissolving one teaspoon of salt, eight teaspoons of sugar and the juice of an orange into one litre of clean water. Studies have shown the efficacy of antibiotics in reducing the duration of the symptoms of infectious enteritis of bacterial origin, however antibiotic treatments are usually not required due to the self-limiting duration of infectious enteritis.
Possible treatments include:
- In stable cases, use of laxatives and bulking agents, as well as modifications in diet and stool habits are effective.
- Corticosteroids and other anti-inflammatory medication is used in toxic megacolon.
- Antibiotics are used for bacterial infections such as oral vancomycin for "Clostridium difficile"
- Disimpaction of feces and decompression using anorectal and nasogastric tubes.
- When megacolon worsens and the conservative measures fail to restore transit, surgery may be necessary.
- Bethanechol can also be used to treat megacolon by means of its direct cholinergic action and its stimulation of muscarinic receptors which bring about a parasympathetic like effect.
There are several surgical approaches to treat megacolon, such as a colectomy (removal of the entire colon) with ileorectal anastomosis (ligation of the remaining ileum and rectum segments), or a total proctocolectomy (removal of colon, sigmoid and rectum) followed by ileostomy or followed by ileoanal anastomosis.
Typhlitis is a medical emergency and requires prompt management. Untreated typhlitis has a poor prognosis, particularly if associated with pneumatosis intestinalis (air in the bowel wall) and/or bowel perforation, and has significant morbidity unless promptly recognized and aggressively treated.
Successful treatment hinges on:
1. Early diagnosis provided by a high index of suspicion and the use of CT scanning
2. Nonoperative treatment for uncomplicated cases
3. Empiric antibiotics, particularly if the patient is neutropenic or at other risk of infection.
In rare cases of prolonged neutropenia and complications such as bowel perforation, neutrophil transfusions can be considered but have not been studied in a randomized control trial. Elective right hemicolectomy may be used to prevent recurrence but is generally not recommended
"...The authors have found nonoperative treatment highly effective in patients who do not manifest signs of peritonitis, perforation, gastrointestinal hemorrhage, or clinical deterioration. Recurrent typhlitis was frequent after conservative therapy (recurrence rate, 67 percent), however," as based on studies from the 1980s
Treatment for colitis-X usually does not save the horse. The prognosis is average to poor, and mortality is 90% to 100%. However, treatments are available, and one famous horse that survived colitis-X was U.S. Triple Crown winner Seattle Slew, that survived colitis-X in 1978 and went on to race as a four-year-old.
Large amounts of intravenous fluids are needed to counter the severe dehydration, and electrolyte replacement is often necessary. Flunixin meglumine (Banamine) may help block the effects of toxemia. Mortality rate has been theorized to fall to 75% if treatment is prompt and aggressive, including administration of not only fluids and electrolytes, but also blood plasma, anti-inflammatory and analgesic drugs, and antibiotics. Preventing dehydration is extremely important. Nutrition is also important. Either parenteral or normal feeding can be used to support the stressed metabolism of the sick horse. Finally, the use of probiotics is considered beneficial in the restoration of the normal intestinal flora. The probiotics most often used for this purpose contain "Lactobacillus" and "Bifidobacterium".
Endotoxemia is a serious complication of colic and warrants aggressive treatment. Endotoxin (lipopolysaccharide) is released from the cell wall of gram-negative bacteria when they die. Normally, endotoxin is prevented from entering systemic circulation by the barrier function of the intestinal mucosa, antibodies and enzymes which bind and neutralize it and, for the small amount that manages to enter the blood stream, removal by Kupffer cells in the liver. Endotoxemia occurs when there is an overgrowth and secondary die-off of gram negative bacteria, releasing mass quantities of endotoxin. This is especially common when the mucosal barrier is damaged, as with ischemia of the GI tract secondary to a strangulating lesion or displacement. Endotoxemia produces systemic effects such as cardiovascular shock, insulin resistance, and coagulation abnormalities.
Fluid support is essential to maintain blood pressure, often with the help of colloids or hypertonic saline. NSAIDs are commonly given to reduce systemic inflammation. However, they decrease the levels of certain prostaglandins that normally promote healing of the intestinal mucosa, which subsequently increases the amount of endotoxin absorbed. To counteract this, NSAIDs are sometimes administered with a lidocaine drip, which appears to reduce this particular negative effect. Flunixin may be used for this purpose at a dose lower than that used for analgesia, so can be safely given to a colicky horse without risking masking signs that the horse requires surgery. Other drugs that bind endotoxin, such as polymyxin B and Bio-Sponge, are also often used. Polymixin B prevents endotoxin from binding to inflammatory cells, but is potentially nephrotoxic, so should be used with caution in horses with azotemia, especially neonatal foals. Plasma may also be given with the intent of neutralizing endotoxin.
Laminitis is a major concern in horses suffering from endotoxemia. Ideally, prophylactic treatment should be provided to endotoxic horses, which includes the use of NSAIDs, DMSO, icing of the feet, and frog support. Horses are also sometimes administered heparin, which is thought to reduce the risk of laminitis by decreasing blood coagulability and thus blood clot formation in the capillaries of the foot.
In addition to fluid support, impactions are often treated with intestinal lubricants and laxatives to help move the obstruction along. Mineral oil is the most commonly used lubricant for large colon impactions, and is administered via nasogastric tube, up to 4 liters once or twice daily. It helps coat the intestine, but is not very effective for severe impactions or sand colic since it may simply bypass the obstruction. Mineral oil has the added benefit of crudely measuring GI transit time, a process which normally takes around 18 hours, since it is obvious when it is passed. The detergent dioctyl sodium sulfosuccinate (DDS) is also commonly given in oral fluids. It is more effective in softening an impaction than mineral oil, and helps stimulate intestinal motility, but can inhibit fluid absorption from the intestine and is potentially toxic so is only given in small amounts, two separate times 48 hours apart. Epsom salts are also useful for impactions, since they act both as an osmotic agent, to increase fluid in the GI tract, and as a laxative, but do run the risk of dehydration and diarrhea. Strong laxatives are not recommended for treating impactions.
Treatment consists primarily of supportive care including providing bowel rest by stopping enteral feeds, gastric decompression with intermittent suction, fluid repletion to correct electrolyte abnormalities and third-space losses, support for blood pressure, parenteral nutrition, and prompt antibiotic therapy. Monitoring is clinical, although serial supine and left lateral decubitus abdominal x-rays should be performed every six hours. Where the disease is not halted through medical treatment alone, or when the bowel perforates, immediate emergency surgery to resect the dead bowel is generally required, although abdominal drains may be placed in very unstable infants as a temporizing measure. Surgery may require a colostomy, which may be able to be reversed at a later time. Some children may suffer from short bowel syndrome if extensive portions of the bowel had to be removed.
There is no cure for short bowel syndrome except transplant. In newborn infants, the 4-year survival rate on parenteral nutrition is approximately 70%. In newborn infants with less than 10% of expected intestinal length, 5 year survival is approximately 20%. Some studies suggest that much of the mortality is due to a complication of the total parenteral nutrition (TPN), especially chronic liver disease. Much hope is vested in Omegaven, a type of lipid TPN feed, in which recent case reports suggest the risk of liver disease is much lower.
Although promising, small intestine transplant has a mixed success rate, with postoperative mortality rate of up to 30%. One-year and 4-year survival rate are 90% and 60%, respectively.
Once a child is born prematurely, thought must be given to decreasing the risk for developing NEC. Toward that aim, the methods of providing hyperalimentation and oral feeds are both important. In a 2012 policy statement, the American Academy of Pediatrics recommended feeding preterm infants human milk, finding "significant short- and long-term beneficial effects," including reducing the rate of NEC by a factor of two or more.
A study by researchers in Peoria, IL, published in "Pediatrics" in 2008, demonstrated that using a higher rate of lipid (fats and/or oils) infusion for very low birth weight infants in the first week of life resulted in zero infants developing NEC in the experimental group, compared with 14% with NEC in the control group. (They started the experimental group at 2 g/kg/d of 20% IVFE and increased within two days to 3 g/kg/d; amino acids were started at 3 g/kg/d and increased to 3.5.)
Neonatologists at the University of Iowa reported on the importance of providing small amounts of trophic oral feeds of human milk starting as soon as possible, while the infant is being primarily fed intravenously, in order to prime the immature gut to mature and become ready to receive greater oral intake. Human milk from a milk bank or donor can be used if mother's milk is unavailable. The gut mucosal cells do not get enough nourishment from arterial blood supply to stay healthy, especially in very premature infants, where the blood supply is limited due to immature development of the capillaries, so nutrients from the lumen of the gut are needed.
A Cochrane review published in April 2014 has established that supplementation of probiotics enterally "prevents severe NEC as well as all-cause mortality in preterm infants."
Increasing amounts of milk by 30 to 40 ml/kg is safe in infant who are born weighing very little. Not beginning feeding an infant by mouth for more than 4 days does not appear to have protective benefits.
Data from the NICHD Neonatal Research Network's Glutamine Trial showed that the incidence of NEC among extremely low birthweight (ELBW, <1000 g) infants fed with more than 98% human milk from their mothers was 1.3%, compared with 11.1% among infants fed only preterm formula, and 8.2% among infants fed a mixed diet, suggesting that infant deaths could be reduced by efforts to support production of milk by mothers of ELBW newborns.
Research from the University of California, San Diego found that higher levels of one specific human milk oligosaccharide, disialyllacto-N-tetraose, may be protective against the development of NEC.
Specific types of enterocolitis include:
- necrotizing enterocolitis (most common in premature infants)
- pseudomembranous enterocolitis (also called "Pseudomembranous colitis")
Inflammation can spread to other parts of the gut in patients with typhlitis. The condition can also cause the cecum to become distended and can cut off its blood supply. This and other factors can result in necrosis and perforation of the bowel, which can cause peritonitis and sepsis.
Historically, the mortality rate for typhlitis was as high as 50%, mostly because it is frequently associated with bowel perforation. More recent studies have demonstrated better outcomes with prompt medical management, generally with resolution of symptoms with neutrophil recovery without death
The first stage of treatment used to be a reversible colostomy. In this approach, the healthy end of the large intestine is cut and attached to an opening created on the front of the abdomen. The contents of the bowel are discharged through the hole in the abdomen and into a bag. Later, when the patient's weight, age, and condition are right, the "new" functional end of the bowel is connected with the anus. The first surgical treatment involving surgical resection followed by reanastomosis without a colostomy occurred as early as 1933 by Doctor Baird in Birmingham on a one-year-old boy.
Enterocolitis or coloenteritis is an inflammation of the digestive tract, involving enteritis of the small intestine and colitis of the colon. It may be caused by various infections, with bacteria, viruses, fungi, parasites, or other causes. Common clinical manifestations of enterocolitis are frequent diarrheal defecations, with or without nausea, vomiting, abdominal pain, fever, chills, alteration of general condition. General manifestations are given by the dissemination of the infectious agent or its toxins throughout the body, or – most frequently – by significant losses of water and minerals, the consequence of diarrhea and vomiting.
Among the causal agents of acute enterocolitis are:
- bacteria: "Salmonella", "Shigella", "Escherichia coli", "Campylobacter" etc.;
- viruses: enteroviruses, rotaviruses, Norwalk virus, adenoviruses;
- fungi: candidiasis, especially in immunosuppressed patients or who have previously received prolonged antibiotic treatment;
- parasites: "Giardia lamblia" (with high frequency of infestation in the population, but not always with clinical manifestations), "Balantidium coli", "Blastocystis homnis", "Cryptosporidium" (diarrhea in people with immunosuppression), "Entamoeba histolytica" (produces the amebian dysentery, common in tropical areas).
Treatment of Hirschsprung's disease consists of surgical removal (resection) of the abnormal section of the colon, followed by reanastomosis.
Crohn's disease – also known as regional enteritis, it can occur along any surface of the gastrointestinal tract. In 40% of cases it is limited to the small intestine.
Coeliac disease – caused by an autoimmune reaction to gluten by genetically predisposed individuals.
Eosinophilic enteropathy – a condition where eosinophils build up in the gastrointestinal tract and blood vessels, leading to polyp formation, necrosis, inflammation and ulcers. It is most commonly seen in patients with a history of atopy, however is overall relatively uncommon.
Neutropenic vs non-neutropenic candidemia is treated differently.
An intravenous echinocandin such as anidulafungin, caspofungin or micafungin is recommended as first-line therapy for fungemia, specifically candidemia. Oral or intravenous fluconazole is an acceptable alternative. The lipid formulation amphotericin B is a reasonable alternative if there is limited antifungal availability, antifungal resistance, or antifungal intolerance.
Gastroschisis requires surgical treatment to return the exposed intestines to the abdominal cavity and close the hole in the abdomen. Sometimes this is done immediately but more often the exposed organs are covered with sterile drapings, and only later is the surgery done. Affected newborns frequently require more than one surgery, as only about 10% of cases can be closed in a single surgery.
Given the urgent need for surgery after birth, it is recommended that delivery occur at a facility equipped for caring for these high-risk neonates, as transfers to other facilities may increase risk of adverse outcomes. There is no evidence that cesarean deliveries lead to better outcomes for babies with gastroschisis, so cesarean delivery is only considered if there are other indications.
The main cause for lengthy recovery periods is the time taken for the infant's bowel function to return to normal. After surgery infants are fed through IV fluids and gradually introduced to normal feeding.
Note that, in neonates, sepsis is difficult to diagnose clinically. They may be relatively asymptomatic until hemodynamic and respiratory collapse is imminent, so, if there is even a remote suspicion of sepsis, they are frequently treated with antibiotics empirically until cultures are sufficiently proven to be negative. In addition to fluid resuscitation and supportive care, a common antibiotic regimen in infants with suspected sepsis is a beta-lactam antibiotic (usually ampicillin) in combination with an aminoglycoside (usually gentamicin) or a third-generation cephalosporin (usually cefotaxime—ceftriaxone is generally avoided in neonates due to the theoretical risk of kernicterus.) The organisms which are targeted are species that predominate in the female genitourinary tract and to which neonates are especially vulnerable to, specifically Group B Streptococcus, "Escherichia coli", and "Listeria monocytogenes" (This is the main rationale for using ampicillin versus other beta-lactams.) Of course, neonates are also vulnerable to other common pathogens that can cause meningitis and bacteremia such as "Streptococcus pneumoniae" and "Neisseria meningitidis". Although uncommon, if anaerobic species are suspected (such as in cases where necrotizing enterocolitis or intestinal perforation is a concern, clindamycin is often added.
Granulocyte-macrophage colony stimulating factor (GM-CSF) is sometimes used in neonatal sepsis. However, a 2009 study found that GM-CSF corrects neutropenia if present but it has no effect on reducing sepsis or improving survival.
Trials of probiotics for prevention of neonatal sepsis have generally been too small and statistically underpowered to detect any benefit, but a randomized controlled trial that enrolled 4,556 neonates in India reported that probiotics significantly reduced the risk of developing sepsis. The probiotic used in the trial was "Lactobacillus plantarum".
A very large meta-analysis investigated the effect of probiotics on preventing late-onset sepsis (LOS) in neonates. Probiotics were found to reduce the risk of LOS, but only in babies who were fed human milk exclusively. It is difficult to distinguish if the prevention was a result of the probiotic supplementation or if it was a result of the properties of human milk. It is also still unclear if probiotic administration reduces LOS risk in extremely low birth weight infants due to the limited number of studies that investigated it. Out of the 37 studies included in this systematic review, none indicated any safety problems related to the probiotics. It would be beneficial to clarify the relationship between probiotic supplementation and human milk for future studies in order to prevent late onset sepsis in neonates.
Diseases of the hepatobiliary system affect the biliary tract (also known as the "biliary tree"), which secretes bile in order to aid digestion of fats. Diseases of the gallbladder and bile ducts are commonly diet-related, and may include the formation of gallstones that impact in the gallbladder (cholecystolithiasis) or in the common bile duct (choledocholithiasis).
Gallstones are a common cause of inflammation of the gallbladder, called cholecystitis. Inflammation of the biliary duct is called cholangitis, which may be associated with autoimmune disease, such as primary sclerosing cholangitis, or a result of bacterial infection, such as ascending cholangitis.
Disease of the biliary tree may cause pain in the upper right abdomen, particularly when pressed. Disease might be investigated using ultrasound or ERCP, and might be treated with drugs such as antibiotics or UDCA, or by the surgical removal of the gallbladder.
Risperidone, an anti-psychotic medication, can result in megacolon.
Pneumatosis intestinalis (also called intestinal pneumatosis, pneumatosis cystoides intestinalis, or pneumatosis coli) is of an intestine, that is, gas cysts in the bowel wall. As a radiological sign it is highly suggestive for necrotizing enterocolitis. This is in contrast to gas in the intestinal lumen (which is relieved by flatulence). In newborns, pneumatosis intestinalis is considered diagnostic for necrotizing enterocolitis, and the air is produced by bacteria in the bowel wall. The pathogenesis of pneumatosis intestinalis is poorly understood and is likely multifactorial. PI itself is not a disease, but rather a clinical sign. In some cases, PI is an incidental finding, whereas in others, it portends a life-threatening intra-abdominal condition.
Recombinant granulocyte-colony stimulating factor preparations, such as filgrastim can be effective in patients with congenital forms of neutropenia including severe congenital neutropenia and cyclic neutropenia, the amount needed (dosage) varies considerably (depending on the individual's condition) to stabilize the neutrophil count. Guidelines for neutropenia regarding diet are currently being studied.
Most cases of neonatal neutropenia are temporary. Antibiotic prophylaxis is not recommended because of the possibility of encouraging the development of multidrug-resistant bacterial strains.
Neutropenia can be treated with hematopoietic Growth Factors, granulocyte-colony stimulating factor (G-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF). These are cytokines (inflammation-inducing chemicals) that are present naturally in the body. These factors are used regularly in cancer treatment with adults and children. The factors promote neutrophil recovery following anticancer therapy.
The administration of intravenous immunoglobulins (IVIGs) has had some success in treating neutropenias of alloimmune and autoimmune origins with a response rate of about 50%. Blood transfusions have not been effective.