Typhlitis
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Synonyms and keywords: neutropenic colitis; neutropenic enterocolitis; cecitis
Overview
Typhlitis occurs in neutropenic patients undergoing treatment for a malignancy, most frequently patients with acute leukemia who are receiving chemotherapy. It has also been reported in patients with aplastic anemia, lymphoma, or acquired immunodeficiency syndrome and after kidney transplantation. Typhlitis is characterized by edema and inflammation of the cecum, the ascending colon, and sometimes the terminal ileum. The inflammation can be so severe that transmural necrosis, perforation, and death can result. The mechanism of the condition is not known, but it is probably due to a combination of ischemia, infection (especially with cytomegalovirus), mucosal hemorrhage, and perhaps neoplastic infiltration. Treatment consists of bowel rest, total parenteral nutrition, antibiotics, and aggressive fluid and electrolyte replacement.
Historical Perspective
[Disease name] was first discovered by [name of scientist], a [nationality + occupation], in [year]/during/following [event].
The association between [important risk factor/cause] and [disease name] was made in/during [year/event].
In [year], [scientist] was the first to discover the association between [risk factor] and the development of [disease name].
In [year], [gene] mutations were first implicated in the pathogenesis of [disease name].
There have been several outbreaks of [disease name], including -----.
In [year], [diagnostic test/therapy] was developed by [scientist] to treat/diagnose [disease name].
Classification
There is no established system for the classification of typhlitis.
Pathophysiology
- The exact pathogenesis of neutropenic enterocolitis is not fully understood.
- Intestinal mucosal damage, neutropenia, and the immunocompromised status of the afflicted patients appear to be the key factors in disease initiation.
- Intestinal edema, engorged veins, and a disturbed mucosal surface result from these early circumstances, making the mucosa more prone to bacterial intramural invasion.
- The intestinal motility is affected by the distension and necrosis caused directly by chemotherapeutic agents.
- 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.[1]
- Gram-negative rods, gram-positive cocci, enterococci, fungi, and viruses have all been blamed for the outbreak.[2][3]
Causes by Organ System
| Cardiovascular | No underlying causes |
| Chemical/Poisoning | No underlying causes |
| Dental | No underlying causes |
| Dermatologic | No underlying causes |
| Drug Side Effect | Doxorubicin Hydrochloride, Sulfasalazine |
| Ear Nose Throat | No underlying causes |
| Endocrine | No underlying causes |
| Environmental | No underlying causes |
| Gastroenterologic | No underlying causes |
| Genetic | No underlying causes |
| Hematologic | No underlying causes |
| Iatrogenic | No underlying causes |
| Infectious Disease | No underlying causes |
| Musculoskeletal/Orthopedic | No underlying causes |
| Neurologic | No underlying causes |
| Nutritional/Metabolic | No underlying causes |
| Obstetric/Gynecologic | No underlying causes |
| Oncologic | No underlying causes |
| Ophthalmologic | No underlying causes |
| Overdose/Toxicity | No underlying causes |
| Psychiatric | No underlying causes |
| Pulmonary | No underlying causes |
| Renal/Electrolyte | No underlying causes |
| Rheumatology/Immunology/Allergy | No underlying causes |
| Sexual | No underlying causes |
| Trauma | No underlying causes |
| Urologic | No underlying causes |
| Miscellaneous | No underlying causes |
Causes in Alphabetical Order
Differentiating Typhlitis from other Diseases
Typhlitis must be distinguished from other diseases characterized by fever, abdominal pain, and diarrhea. Before diagnosing this condition, some diseases with similar clinical manifestations should be ruled out.
- Clostridium difficile infection[4]
- Cytomegalovirus colitis[5]
- Norovirus infection[6]
- Graft versus host disease[7]
- Acute appendicitis[8]
- Ischemic colitis[9]
Epidemiology and Demographics
The prevalence of neutropenic enterocolitis varies between studies. Gorschlüter 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.[10][11]
- 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.[12]
Risk Factors
Common risk factors in the development of typhlitis include hematological, solid tumors, neutropenic and Immunocompromised individuals.[13]
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.
- Prognosis is generally poor, and the mortality rate of patients with Neutropenic enterocolitis is as high as 50% especially in patients with transmural inflammation or intestinal perforation.[14][15]
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 ocur 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.[16]
Laboratory Findings??
There are no diagnostic laboratory findings associated with Typhlitis. (neutropenia, thrombocytopenia or coagulopathy)
Electrocardiogram
There are no ECG findings associated with Typhlitis
Echocardiography
There are no echocardiography associated with neutropenic colitis.
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.[17]
CT Abdomen
- 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.[18]
Other Imaging Findings/Ultrasound Abdomen
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 .[19]
Life Threatening Causes
Life-threatening causes include conditions such as pneumatosis, pneumoperitoneum, and pericolic fluid collections is important because they indicate a need for urgent surgical management
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.[20][21]
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[22].
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.
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
References
- ↑ Cloutier RL (2009). "Neutropenic enterocolitis". Emerg Med Clin North Am. 27 (3): 415–22. doi:10.1016/j.emc.2009.04.002. PMID 19646645.
- ↑ Rodrigues FG, Dasilva G, Wexner SD (2017). "Neutropenic enterocolitis". World J Gastroenterol. 23 (1): 42–47. doi:10.3748/wjg.v23.i1.42. PMC 5221285. PMID 28104979.
- ↑ "StatPearls". ( ). 2021: . PMID 31869058.
- ↑ Czepiel J, Dróżdż M, Pituch H, Kuijper EJ, Perucki W, Mielimonka A; et al. (2019). "Clostridium difficile infection: review". Eur J Clin Microbiol Infect Dis. 38 (7): 1211–1221. doi:10.1007/s10096-019-03539-6. PMC 6570665 Check
|pmc=value (help). PMID 30945014. - ↑ Pillet S, Pozzetto B, Roblin X (2016). "Cytomegalovirus and ulcerative colitis: Place of antiviral therapy". World J Gastroenterol. 22 (6): 2030–45. doi:10.3748/wjg.v22.i6.2030. PMC 4726676. PMID 26877608.
- ↑ "StatPearls". 2021. PMID 31335045.
- ↑ Ramachandran V, Kolli SS, Strowd LC (2019). "Review of Graft-Versus-Host Disease". Dermatol Clin. 37 (4): 569–582. doi:10.1016/j.det.2019.05.014. PMID 31466596.
- ↑ Bhangu A, Søreide K, Di Saverio S, Assarsson JH, Drake FT (2015). "Acute appendicitis: modern understanding of pathogenesis, diagnosis, and management". Lancet. 386 (10000): 1278–1287. doi:10.1016/S0140-6736(15)00275-5. PMID 26460662.
- ↑ Theodoropoulou A, Koutroubakis IE (2008). "Ischemic colitis: clinical practice in diagnosis and treatment". World J Gastroenterol. 14 (48): 7302–8. doi:10.3748/wjg.14.7302. PMC 2778113. PMID 19109863.
- ↑ Gorschlüter M, Mey U, Strehl J, Ziske C, Schepke M, Schmidt-Wolf IG; et al. (2005). "Neutropenic enterocolitis in adults: systematic analysis of evidence quality". Eur J Haematol. 75 (1): 1–13. doi:10.1111/j.1600-0609.2005.00442.x. PMID 15946304.
- ↑ Aksoy DY, Tanriover MD, Uzun O, Zarakolu P, Ercis S, Ergüven S; et al. (2007). "Diarrhea in neutropenic patients: a prospective cohort study with emphasis on neutropenic enterocolitis". Ann Oncol. 18 (1): 183–189. doi:10.1093/annonc/mdl337. PMID 17023562.
- ↑ Nesher L, Rolston KV (2013). "Neutropenic enterocolitis, a growing concern in the era of widespread use of aggressive chemotherapy". Clin Infect Dis. 56 (5): 711–7. doi:10.1093/cid/cis998. PMID 23196957.
- ↑ Biasoli, I; Nucci, M; Spector, N; Portugal, R; Domingues, A; Pulcheri, W (1997). "Risk factors for typhlitis". Oncology Reports. doi:10.3892/or.4.5.1029. ISSN 1021-335X.
- ↑ Gorschlüter M, Mey U, Strehl J, Ziske C, Schepke M, Schmidt-Wolf IG; et al. (2005). "Neutropenic enterocolitis in adults: systematic analysis of evidence quality". Eur J Haematol. 75 (1): 1–13. doi:10.1111/j.1600-0609.2005.00442.x. PMID 15946304.
- ↑ Wade DS, Nava HR, Douglass HO (1992). "Neutropenic enterocolitis. Clinical diagnosis and treatment". Cancer. 69 (1): 17–23. doi:10.1002/1097-0142(19920101)69:1<17::aid-cncr2820690106>3.0.co;2-x. PMID 1727660.
- ↑ Nesher, L.; Rolston, K. V. I. (2012). "Neutropenic Enterocolitis, a Growing Concern in the Era of Widespread Use of Aggressive Chemotherapy". Clinical Infectious Diseases. 56 (5): 711–717. doi:10.1093/cid/cis998. ISSN 1058-4838.
- ↑ Wade DS, Nava HR, Douglass HO (1992). "Neutropenic enterocolitis. Clinical diagnosis and treatment". Cancer. 69 (1): 17–23. doi:10.1002/1097-0142(19920101)69:1<17::aid-cncr2820690106>3.0.co;2-x. PMID 1727660.
- ↑ Kirkpatrick, Iain D. C.; Greenberg, Howard M. (2003). "Gastrointestinal Complications in the Neutropenic Patient: Characterization and Differentiation with Abdominal CT". Radiology. 226 (3): 668–674. doi:10.1148/radiol.2263011932. ISSN 0033-8419.
- ↑ Tamburrini, Stefania; Setola, Francesca Rosa; Belfiore, Maria Paola; Saturnino, Pietro Paolo; Della Casa, Maria Gabriella; Sarti, Giuseppe; Abete, Roberta; Marano, Ines (2018). "Ultrasound diagnosis of typhlitis". Journal of Ultrasound. 22 (1): 103–106. doi:10.1007/s40477-018-0333-2. ISSN 1876-7931.
- ↑ Freifeld AG, Bow EJ, Sepkowitz KA, Boeckh MJ, Ito JI, Mullen CA; et al. (2011). "Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the infectious diseases society of america". Clin Infect Dis. 52 (4): e56–93. doi:10.1093/cid/cir073. PMID 21258094.
- ↑ Salazar R, Solá C, Maroto P, Tabernero JM, Brunet J, Verger G; et al. (1999). "Infectious complications in 126 patients treated with high-dose chemotherapy and autologous peripheral blood stem cell transplantation". Bone Marrow Transplant. 23 (1): 27–33. doi:10.1038/sj.bmt.1701520. PMID 10037047.
- ↑ Shamberger RC, Weinstein HJ, Delorey MJ, Levey RH (1986). "The medical and surgical management of typhlitis in children with acute nonlymphocytic (myelogenous) leukemia". Cancer. 57 (3): 603–9. doi:10.1002/1097-0142(19860201)57:3<603::aid-cncr2820570335>3.0.co;2-k. PMID 3484659.