What is Neutropenic Enterocolitis or Typhlitis?
Neutropenic enterocolitis or typhlitis is a fatal and acute necrotizing enterocolitis which occurs mainly in neutropenic patients. Neutropenic enterocolitis is also known as "ileocecal syndrome," "necrotizing enterocolitis," “typhlenteritis” and less commonly “caecitis orcecitis.” Neutropenic enterocolitis or typhlitis is commonly seen in patients who suffer from hematologic malignancies, who are myelosuppressed and are neutropenic. Being neutropenic means that the patient has decreased levels of neutrophil granulocytes. Such patients will have breakdown of integrity of the gut mucosa due to cytotoxic chemotherapy i.e. treatment taken for cancer. "Typhlitis" is derived from the Greek word "typhlon," which means cecum, where there is neutropenic enterocolitis in the ileocecal region.
Neutropenic enterocolitis or typhlitis patient has inflammation of the cecum, and there can also be inflammation of the ileum or appendix. Inflammation of the cecum usually results in necrosis of the affected structures.
The exact cause of neutropenic enterocolitis or typhlitis is not clearly understood. There are multiple risk factors and some of the potential causes include damage to the mucosal lining of the stomach from injury, infection or cytotoxic drugs. Inflammation of the cecum is an extremely serious condition, as it can lead to widespread infection. Death of the neutropenic enterocolitis or typhlitis patient commonly occurs due to necrosis of the bowel, which is followed by sepsis where there is systemic inflammation in the body.
Initially neutropenic enterocolitis or typhlitis was described in children who were undergoing treatment for (chemotherapy) leukemia. However, during the course of past 3 decades, this condition has been increasingly found in adults who are suffering from different types of solid malignant tumors, myeloproliferative disorders and along with bone marrow and solid organ transplantation due to immunosuppression. In some adults, neutropenic enterocolitis occurs due to increased use of myelotoxic chemotherapeutic regimens.
There are can be dramatic changes in the patient from neutropenic enterocolitis or typhlitis and the result of the disease can be very devastating. The prognosis of neutropenic enterocolitis or typhlitis is very poor with the mortality rates being high, about up to 50% on average. Treatment for neutropenic enterocolitis or typhlitis is quite controversial and comprises of different options which ranges from conservative treatment measures to surgery. It is very important that neutropenic enterocolitis or typhlitis is diagnosed early and the treatment is started immediately for a potentially better prognosis.
Pathophysiology of Neutropenic Enterocolitis or Typhlitis
The exact cause and the methodology of the progression of neutropenic enterocolitis or typhlitis is not clear, however, acute neutropenia appears to be the constant feature. The pathophysiology of neutropenic enterocolitis can only involve cecum, or it can extend to the ascending colon, ileum or both. Distension of the cecum causes restrictive blood supply, which can predispose the cecum more to damage or injury than other structures.
There are various factors which are thought to potentially play a role in the pathogenesis of neutropenic enterocolitis or typhlitis and these comprise of:
Cytotoxic Drugs: Use of cytotoxic drugs which cause injury to the mucosa; however, mucosal injury can also occur in the absence of cytotoxic drug therapy. Neutropenia alone can also cause mucosal ulcerations.
Restricted Blood Supply: Cecal distention causes hindrance to the blood supply which adds to the mucosal damage.
Bacterial Invasion: Bacterial and in some cases, fungal invasion of the impaired wall of the bowel, which can lead to transmural inflammation, resulting in peritonitis and perforation. Patients frequently suffer from complications, such as bacteremia which is a frequent complication and less commonly fungemia.
Medications: Use of certain medications, such as antibiotics and steroids, as they are thought to contribute to changes in the enteric bacterial flora and cause overgrowth of fungi.
Causes & Risk Factors of Neutropenic Enterocolitis or Typhlitis
This condition was initially described in 1960 in patients who were being treated for leukemia. After this time, neutropenic enterocolitis or typhlitis has been found in patients suffering from aplastic anemia, lymphoma, AIDS and also in those patients who were being treated for other types of cancer. Children who are undergoing chemotherapy for leukemia and individuals who are on immunosuppressant therapy after an organ transplant are at an increased risk for neutropenic enterocolitis or typhlitis.
Neutropenic Enterocolitis or Typhlitis is most commonly seen in patients who are immunocompromised, e.g. those patients who are undergoing chemotherapy, suffering with AIDS, organ transplantation and elderly individuals. Cytotoxic chemotherapeutic agents are thought to be responsible for majority of the cases of neutropenic enterocolitis; however, there are other conditions which predispose some people to develop this condition. Some of the cytotoxic chemotherapeutic agents consist of vinca alkaloids, cytosine arabinoside and doxorubicin. There are other drugs which are also thought to be responsible for causing neutropenic enterocolitis and these include docetaxel, paclitaxel, procainamide, 5-fluorouracil, sulfasalazine, vinorelbine, cisplatin, carboplatin, leucovorin and gemcitabine.
Other than this, new cases of neutropenic enterocolitis have come forward which are associated with alemtuzumab which is the monoclonal antibody along with pegylated interferon (PEG-INF) and ribavirin.
Other predisposing factors for neutropenic enterocolitis or typhlitis consist of:
- Bone marrow and solid organ transplantation.
- Myelodysplastic syndromes, aplastic anemia and multiple myeloma.
- Cyclic neutropenia.
- Acquired immunodeficiency syndrome (AIDS).
- Solid malignant tumors.
Signs & Symptoms of Neutropenic Enterocolitis or Typhlitis
The symptoms of Neutropenic Enterocolitis or Typhlitis resemble the symptoms of acute appendicitis, and exhibit a common pattern that includes pain and tenderness in the right lower quadrant of the abdomen, distended abdomen, diarrhea, chills, fever, nausea, vomiting, and abdominal tenderness or pain. Neutropenic enterocolitis or typhlitis patient almost always has neutropenia, where there is reduced level of neutrophils.
Diagnosis of Neutropenic Enterocolitis or Typhlitis
Diagnosis of neutropenic enterocolitis or typhlitis is made with a radiograph CT scan where thickening of the cecum is seen along with "fat stranding.”
Treatment of Neutropenic Enterocolitis or Typhlitis
Neutropenic Enterocolitis or Typhlitis is a medical emergency and carries a very poor prognosis. This condition is life threatening and the outcome is somewhat better only if it is immediately diagnosed and aggressively treated. Successful treatment of Neutropenic Enterocolitis or Typhlitis depends on early diagnosis, which can be done with recognizing the symptoms and CT scans, conservative or non-operative treatment if the case is uncomplicated and elective right hemicolectomy is recommended to prevent recurrence of Neutropenic Enterocolitis. There is no specific treatment for Neutropenic Enterocolitis or Typhlitis. Some practitioners believe in conservative management, whereas others recommend surgery to provide best opportunity for a potentially good outcome. Other than this, the outcome of treatment usually depends more on the condition of the patient rather than treatment method used. So, treatment and outcome differs from patient to patient.
Conservative Management for Neutropenic Enterocolitis or Typhlitis consists of monitoring and treating the symptoms of the patient instead of taking aggressive approach for treating the cause of this condition. Conservative management is thought to be effective in neutropenic enterocolitis or typhlitis patients who do not exhibit signs of gastrointestinal hemorrhage, perforation, peritonitis or clinical deterioration. Conservative treatment of Neutropenic Enterocolitis consists of I.V. feeding and nasogastric suction where the stomach contents are drained through a tube instead of letting them being allowed to enter the bowel. By adopting this treatment method, the bowel is allowed to rest and it helps with healing. Patient is given broad-spectrum antibiotics to help control the infection. Other than this, anti-fungal medications can also be used. Recurrent Neutropenic Enterocolitis or typhlitis, however, was frequently seen after conservative management this condition.
The aggressive or surgical treatment for neutropenic enterocolitis or typhlitis is recommended for those patients who are not responding to conservative treatment strategy. Surgery is usually performed on a patient to patient basis, and the surgeon will often decide on how to proceed with the operation after he/ she has viewed the intra-abdominal region of the patient suffering from neutropenic enterocolitis or typhlitis. Some of the surgical options consist of catheterizing of the cecum to help with drainage and removing a segment of the colon or the entire colon.
Complications of Neutropenic Enterocolitis or Typhlitis
- Gastrointestinal bleeding.
- Perforation of the bowel.
- Gastrointestinal obstruction.
- Intra-abdominal abscess.
Prognosis of Neutropenic Enterocolitis or Typhlitis
The prognosis of neutropenic enterocolitis or typhlitis is often poor, with high mortality rates that average about 45-50%, as this condition is often associated with perforation of the bowel. The prognosis highly depends on the speed at which the white blood cell (WBC) count is restored in the patient. The outcome of neutropenic enterocolitis or typhlitis can be better if this condition is early and accurately diagnosed along with giving aggressive medical and supportive treatment.
The inflammation in neutropenic enterocolitis or typhlitis can spread to other regions of the gut and there can also be distention of the cecum where its blood supply is completely cut off. This along with other factors result in necrosis and bowel perforation, which leads to sepsis and peritonitis which are fatal.