Typhlitis
Synonyms and keywords: Neutropenic colitis; Neutropenic enterocolitis; cecitis

# Overview
Typhlitis is most commonly seen in neutropenic patients receiving chemotherapy for a cancer. It is also been seen in people with aplastic anemia, lymphoma, acquired immunodeficiency syndrome, as well as people who have had a kidney transplant. Typhlitis is distinguished by edema and inflammation of the cecum, ascending colon, and, in some cases, terminal ileum. Transmural necrosis, perforation, and mortality can occur as a result of the inflammation. The exact cause of the condition is unknown, but it is most likely caused by a combination of ischemia, infection (particularly with cytomegalovirus), mucosal hemorrhage, and possibly neoplastic infiltration. The treatment includes bowel rest, parenteral nutrition, antibiotics, and intensive fluid and electrolyte replacement.

# Historical Perspective
- In 1970, Wagner et al found and described typhlitis as necrotizing colitis after autopsy of 191 leukemic children with terminal illness at the Texas Children's Hospital, Baylor College of Medicine, Houston, between 1958 and 1970.

# Classification
- There is no established system for the classification of Typhlitis.

# Pathophysiology
- The precise pathophysiology of Neutropenic enterocolitis is unknown.
- The primary variables in illness beginning appear to be intestinal mucosal injury, neutropenia, and the immunocompromised status of the patients.
- Gram-negative rods, gram-positive cocci, enterococci, fungi, and viruses have all been blamed for the outbreak.
- These early circumstances cause intestinal edema, engorged veins, and a disrupted mucosal surface, making the mucosa more susceptible to bacterial intramural invasion.
- The distension and necrosis generated by chemotherapy drugs directly influence intestinal motility.
- Superimposed infections caused by bacteria,fungi and viruses can also disrupts the already damaged mucosa leading further intestinal edema, distension and necrosis of intestinal layer which lead to intestinal perforation.

# Causes

## Causes by Organ System

# Differentiating Typhlitis from other Diseases
Typhlitis must be distinguished from other diseases that exhibit symptoms such as fever, abdominal pain, and diarrhea.
- 1. Clostridium difficile infection
- 2. Cytomegalovirus colitis
- 3. Norovirus infection
- 4. Graft versus host disease
- 5. Acute appendicitis
- 6. Ischemic colitis

# Epidemiology and Demographics
- The prevalence of Neutropenic enterocolitis varies between studies. Gorschluter et al. conducted a systematic review and found that the incidence rate from 21 studies was 5.3 percent in patients hospitalized for hematological malignancies, high-dose chemotherapy for solid tumors, or aplastic anemia. Another cohort study discovered it in 3.5% of 317 severely neutropenic patients. The prevalence of neutropenic enterocolitis has been increasing in tandem with the increased use of chemotherapy, especially the agents known for causing mucositis.
- Patients with hematologic malignancies are more likely to develop Neutropenic enterocolitis as a result of their underlying malignancy as well as their treatment regimens. Neutropenic enterocolitis has also been reported in patients taking immunosuppressive medications, patients diagnosed with solid tumors and autoimmune conditions.

# Risk Factors
Common risk factors in the development of Typhlitis include hematological, solid tumors, neutropenic and Immunocompromised individuals.

# Screening
There is insufficient evidence to recommend routine screening for Neutropenic enterocolitis.

# Natural History, Complications, and Prognosis
- Common complications of Neutropenic enterocolitis include perforation, peritonitis, sepsis, and abscess formation, which are all caused by the pathology (bowel wall inflammation). Other risks are related to pancytopenia include thrombocytopenia-related extreme bleeding and delayed healing.
- Neutrophilic enterocolitis has documented mortality rates as high as 50%, especially in patients with transmural inflammation or intestinal rupture.

# Diagnosis
Neutropenic enterocolitis is typically diagnosed based on a combination of clinical and radiological findings.

## Diagnostic Study of Choice
There are no established criteria for the diagnosis of typhlitis.

## History and Symptoms
The most common symptoms of typhlitis include fever, abdominal pain, and diarrhea. In severe cases, diarrhea can be bloody. Abdominal distension and paralytic ileus may also occur in patients.

## Physical Examination
Common physical examination of patients with Neutropenic enterocolitis is usually remarkable for Abdominal discomfort which can be diffuse or localized, with the right lower quadrant being the most common location. A rigid abdomen could be an indication of bowel perforation.

## Laboratory Findings
Laboratory findings consistent with the diagnosis of typhlitis include neutropenia with absolute neutrophil count <500 cells/microL, thrombocytopenia ranged from 4000/pl to 120,000/pl.

## Ultrasound
- Ultrasound (US) may be helpful in the diagnosis of Neutropenic enterocolitis. Findings on an ultrasound suggestive of Neutropenic enterocolitis include circumferential wall thickening and prominent submucosa .

## X-ray
An x-ray may be helpful in the diagnosis of Typhlitis but nonspecific. Findings on an x-ray suggestive of Neutropenic enterocolitis include inflated cecum with dilated small bowel loops, can detect free air.

## CT Scan
- A computed tomography (CT) scan of the abdomen may be helpful in the diagnosis of Neutropenic enterocolitis. Findings on CT scan suggestive of Neutropenic enterocolitis include Intestinal wall thickening, mesenteric stranding, intestinal dilatation, pneumatosis, distention and circumferential thickening of the cecal wall.

# Treatment

## Medical Therapy
- The mainstay of treatment for Neutropenic enterocolitis consists of both supportive therapy and antimicrobials
- Supportive therapy for Neutropenic colitis include bowel rest with nasogastric suction, intravenous fluids, and, if necessary, parenteral nutrition.
- Empiric therapy for Neutropenic colitis depends on antimicrobial exposure, bacteremia and local resistance pattern.
- Pipericillin-tazobactum, carbapenam, or an antipseudomonal cephalosporin is recommended among  patients who develop neutropenic colitis and vancomycin is considered in case of mucositis is suspected, which is against gram positive bacteria.

## Surgery
- All individuals with Neutropenic enterocolitis should seek surgical advice as soon as possible.
- Surgery is usually reserved for patients with either bowel perforation, pneumoperitoneum, or persistent gastrointestinal bleeding.

## Primary Prevention
Effective measures for the primary prevention of Neutropenic enterocolitis include early detection and treatment can help to avoid problems and improve outcomes in patients who have undergone intensive chemotherapy or a stem cell transplant.Treatment with G-CSF not only speeds recovery from neutropenia episodes that occur during chemotherapy, but it also reduces the risk of consequences including mucositis.

## Secondary Prevention
Effective measures for the secondary prevention include early surgical evaluation in the management of this condition, as it can be life-saving for some patients who present with a complicated Neutropenic enterocolitis