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Typhlitis

Cecitis

Typhlitis is an acute, inflammatory disease of the bowel that occurs in neutropenic patients.


Presentation

Typhlitis presents 10-14 days after treatment with antineoplastic chemotherapy as it manifests in the setting of neutropenia [6] [7]. The features are fever, nausea, emesis, watery or bloody diarrhea [8], and right lower quadrant pain. Also, mucositis may precede the gastrointestinal symptoms.

Physical exam

Remarkable findings may include rebound tenderness and abdominal distention.

Infectious Mononucleosis
  • We present a unique case of an 8-year-old girl with recently diagnosed infectious mononucleosis having findings consistent with typhlitis on abdominal CT.[ncbi.nlm.nih.gov]
  • mononucleosis or EBV infection Influenza Intestinal spirochetosis Intraabdominal abscess Intracranial venous thrombosis Isosporiasis Kawasaki disease Kikuchis disease and Kimura disease Kingella infection Laryngotracheobronchitis Legionellosis Leishmaniasis[books.google.com]
  • Sigirci A, Akinci A, Ozgen O, Ozen O: Neutropenic enterocolitis (typhlitis) associated with infectious mononucleosis. Pediatr Radiol 2006;36:155–157.[karger.com]
Rigor
  • Adverse side effects are increasingly recognized in patients receiving alemtuzumab, mainly including fever, rigors, nausea/vomiting, skin rash; other severe alemtuzumab-related reactions have also been described, such as lymphopenia and neutropenia leading[ncbi.nlm.nih.gov]
  • […] agent in patients with malignancies such as non-Hodgkin lymphoma, B cell chronic lymphocytic leukemia and T cell prolymphocytic leukemia. 1 – 7 Adverse side effects are increasingly recognized in patients receiving alemtuzumab, mainly including fever, rigors[haematologica.org]
Mucosal Edema
  • edema Microscopic (histologic) description Adherent fibrinopurulent exudate over necrotic and edematous mucosa Microscopic (histologic) images Images hosted on other servers: Colonic stenosis in neutropenic patient Back to top[pathologyoutlines.com]
Abdominal Pain
  • Of these, 97 patients had abdominal pain, and 5 had radiologically proven typhlitis. Nonspecific abdominal pain developed on the 12 /- 11th day posttransplant, whereas patients in whom typhlitis developed were diagnosed on day 15.5 /- 7.[ncbi.nlm.nih.gov]
Abdominal Tenderness
  • The severity of typhlitis was related to the duration of neutropenia and the presence of fever or abdominal tenderness.[ncbi.nlm.nih.gov]
  • […] watery or bloody diarrhea, and abdominal pain, may be localized in right lower quadrant ( Radiographics 2000;20:399 ) May cause perforation and require surgery Severity in childhood cancer is related to duration of neutropenia and presence of fever or abdominal[pathologyoutlines.com]
  • At that time, physical examination revealed increased bowel sounds and diffuse abdominal tenderness with no guarding or rebound.[nature.com]
Right Lower Quadrant Tenderness
  • The classic history of periumbilical pain, with anorexia and nausea, followed by localization of pain in the right lower quadrant is more reliable than right lower quadrant pain itself for diagnosis. 2 Findings of fever, right lower quadrant tenderness[accesspediatrics.mhmedical.com]
  • Typhlitis refers to a clinical syndrome of fever and right lower quadrant tenderness in a neutropenic patient after cytotoxic chemotherapy.[ncbi.nlm.nih.gov]
  • She had abdominal pain and distension, decreased bowel sounds, guarding, and right lower quadrant tenderness without rebound.[nature.com]
Hematochezia
  • Haug Browse recently published Learning/CME Learning/CME View all learning/CME CME Partial Oral versus Intravenous Antibiotic Treatment of Endocarditis Case 4-2019: An 18-Year-Old Man with Abdominal Pain and Hematochezia Bridging the Gap Challenge Yourself[nejm.org]
  • It is uncertain if the cecal abnormality in patient 3 had any role in the development of typhlitis and hematochezia.[nature.com]
Lower Abdominal Pain
  • Occasionally a child complains of right lower abdominal pain while walking, or refuses to stand up or walk. Following the onset of pain, fever, tachycardia, and leukocytosis are commonly observed.[accesspediatrics.mhmedical.com]
Hypotension
  • Frequent symptoms were: abdominal pain and tenderness (100% each); fever and nausea (90% each); emesis (80%); diarrhea (50%), and hypotension, peritonitis and abdominal distension (10% each).[ncbi.nlm.nih.gov]
  • Suspected culprits: Drug-induced GI ulcerations Neutropenia leading to invasive bacteria related mucosa damage Sepsis-induced hypotension leading to bowel ischemia Combination of all… Initially, the presenting symptoms can be very nonspecific : Crampy[pedemmorsels.com]
Renal Insufficiency
  • However, oral contrast is sometimes not tolerated in patients with severe gastrointestinal tract symptoms, and IV contrast is typically avoided in patients with renal insufficiency.[radiologypics.com]
Asthenia
  • […] stefania.rizzo@ieo.it A 57-year-old Caucasian male with a history of diffuse large B-cell non-Hodgkin's lymphoma (NHL), who underwent many different cycles of immunochemotherapy during the period May–December 2009, was referred to our Institution for asthenia[ecancer.org]

Workup

Clinical assessment consists of the patient's history, physical exam, and the appropriate tests.

Laboratory tests

Neutropenia is confirmed through a complete blood cell (CBC) count, which is a critical test. Blood cultures, clostridium difficile toxin studies and stool cultures are also obtained. Additionally, a complete metabolic panel and arterial blood gas (ABG) should be performed to rule out acidosis.

Imaging

Computed tomography (CT) is the diagnostic technique of choice. This demonstrates critical features such as diffuse mucosal thickening, edematous colon, and bowel inflammation [9] [10]. Ultrasonography is also used but its results are nonspecific and may display mucosal thickening of the ileum and cecum [10]. Plain abdominal x-rays are not helpful as this modality yields nonspecific findings.

Procedures

A colonoscopy typically reveals edema, mucosal erythema, and ulcerations [11]. Another procedure, flexible sigmoidoscopy, may be performed to rule out other pathologies. However, these procedures are associated with complications and are therefore relatively contraindicated.

Pneumoperitoneum
  • Two patients (17%) in whom CT scans were not obtained underwent surgery for presumed appendicitis and pneumoperitoneum, respectively. Typhlitis was found incidentally.[ncbi.nlm.nih.gov]
  • Findings CT is study of choice Cecal distension and circumferential thickening of cecal wall Mesenteric fat stranding secondary to inflammation Submucosal bowel wall edema Paralytic ileus Terminal ileum and ascending colon may also be affected Pneumatosis, pneumoperitoneum[learningradiology.com]
  • CT scanning readily identifies complications, including pneumatosis coli, pneumoperitoneum, pericolonic fluid collections, and abscess. These complications may require urgent surgical management.[emedicine.medscape.com]
Giardia Lamblia
  • Stool cultures were negative for enteric rods but direct examination of fresh stool revealed the presence of Giardia lamblia. Abdominal pain and diarrhoea developed very rapidly while the patient was only moderately neutropenic.[ncbi.nlm.nih.gov]
Colonic Ulcer
  • Neutropenic enterocolitis (typhlitis) is an unusual acute complication of neutropenia, most often associated with leukaemia and lymphoma and characterized by segmental caecal and ascending colonic ulceration that may progress to necrosis, perforation,[ncbi.nlm.nih.gov]
  • ulceration that may progress to necrosis, perforation, and septicaemia.[link.springer.com]
  • Microscopically, numerous amoebic trophozoites were present in the necrotic debris of the colon ulcers in all cases [Figure 3].[atmph.org]

Treatment

Patients with typhlitis are admitted to the intensive care unit (ICU) and managed conservatively with serial abdominal exams, nasogastric suction, administration of intravenous (IV) fluids, and transfusion of blood products as needed. A key component of the therapy is treatment with broad-spectrum antibiotics that include anaerobic coverage [12] [13]. Also, granulocyte colony-stimulating factor (G-CSF) may be used in patients with significant neutropenia although it has not demonstrated benefit [14].

Surgery is reserved for patients with persistent GI hemorrhage after correction of neutropenia, intraperitoneal perforation, clinical deterioration indicative of sepsis, and the development of an acute abdominal condition that warrants surgical intervention [12] [15].

Note that narcotics, anticholinergic drugs, and anti-diarrheal medications should be avoided in patients with typhlitis.

Prognosis

Early diagnosis and aggressive treatment can improve the outcome [5], which depends on prompt correction of the white blood cell (WBC) count. The mortality rate is 40% to 50% due to severe complications such as bowel perforation, gastrointestinal (GI) hemorrhage, GI obstruction, abdominal abscess, and sepsis.

Etiology

Most cases of typhlitis are caused by cytotoxic chemotherapeutic drugs, particularly in those with acute myelogenous leukemia (AML) and acute lymphoblastic leukemia (ALL) [2] or malignancies in the breast, ovary, lung, and colorectum [1] [3].

Epidemiology

Typhlitis is most prevalent in patients with immunocompromised states, especially in those undergoing chemotherapy.

Sex distribution
Age distribution

Pathophysiology

The cecum is susceptible to this condition due to its poor perfusion, microbial colonization, and lymphatic drainage [4]. The ileum and/or ascending colon may also be affected. With regards to the pathophysiology, it is thought that cytotoxic agents cause direct mucosal injury and neutropenia. The latter allows for overgrowth of enteric bacteria, in which endotoxins cause mucosal damage and ischemia [4].

Prevention

Antibiotic prophylaxis in neutropenic patients may be helpful.

Summary

Typhlitis, also called neutropenic enterocolitis, is a necrotizing disease that affects the cecum and possibly other bowel segments in patients who recently received chemotherapy or those with an immunocompromised condition. This disease should be suspected in patients presenting with neutropenia, fever, and abdominal pain [1]. The diagnosis is achieved through the patient's history, physical exam, and the proper imaging studies. Patients are usually managed conservatively; surgery may occasionally be indicated.

Patient Information

Typhlitis is a condition that develops in patients with weakened immune systems who are receiving chemotherapy for cancer. The symptoms are abdominal pain, fever, nausea, vomiting, diarrhea, etc. It is diagnosed through the history, physical exam, and imaging tests. Patients with this disease are treated with bowel rest, antibiotics, and other conservative measures unless surgery is necessary.

References

Article

  1. Cloutier RL. Neutropenic enterocolitis. Emergency Medicine Clinics of North America. 2009; 27(3):415-22.
  2. Dosik GM, Luna M, Valdivieso M, et al. Necrotizing colitis in patients with cancer. American Journal of Medicine. 1979; 67(4):646-56.
  3. Oehadian A, Fadjari TH. Neutropenic enterocolitis in breast cancer patient after taxane-containing chemotherapy. Acta Medica Indonesiana. 2008;40(1):29-33.
  4. Keidan RD, Fanning J, Gatenby RA, Weese JL. Recurrent typhlitis. A disease resulting from aggressive chemotherapy. Diseases of the Colon & Rectum. 1989;32(3):206-9.
  5. Mullassery D, Bader A, Battersby AJ, et al. Diagnosis, incidence, and outcomes of suspected typhlitis in oncology patients--experience in a tertiary pediatric surgical center in the United Kingdom. Journal of Pediatric Surgery. 2009; 44(2):381-5.
  6. Avigan D, Richardson P, Elias A, et al. Neutropenic enterocolitis as a complication of high dose chemotherapy with stem cell rescue in patients with solid tumors: a case series with a review of the literature. Cancer. 1998; 83(3):409-14.
  7. Ibrahim NK, Sahin AA, Dubrow RA, et al. Colitis associated with docetaxel-based chemotherapy in patients with metastatic breast cancer. Lancet. 2000; 355(9200):281-3.
  8. Katz JA, Wagner ML, Gresik MV, Mahoney DH Jr, Fernbach DJ. Typhlitis. An 18-year experience and postmortem review. Cancer. 1990;65(4):1041-7.
  9. Gorschlüter M, Mey U, Strehl J, et al. Neutropenic enterocolitis in adults: systematic analysis of evidence quality. European Journal of Haematology. 2005;75(1):1-13.
  10. Cartoni C, Dragoni F, Micozzi A, et al. Neutropenic enterocolitis in patients with acute leukemia: prognostic significance of bowel wall thickening detected by ultrasonography. Journal of Clinical Oncology. 2001;19(3):756-61.
  11. Gootenberg JE, Abbondanzo SL. Rapid diagnosis of neutropenic enterocolitis (typhlitis) by ultrasonography. American Journal of Pediatric Hematolology and Oncology. 1987;9(3):222-7.
  12. McNamara MJ, Chalmers AG, Morgan M, Smith SE. Typhlitis in acute childhood leukaemia: radiological features. Clinical Radiology. 1986;37(1):83-6.
  13. Shamberger RC, Weinstein HJ, Delorey MJ, Levey RH. The medical and surgical management of typhlitis in children with acute nonlymphocytic (myelogenous) leukemia. Cancer. 1986;57(3):603-9.
  14. Greil R, Psenak O, Roila F. ESMO Guidelines Working Group. Hematopoietic growth factors: ESMO recommendations for the applications. Annals of Oncology. 2008;19 (Suppl 2):ii116-8.
  15. Bradley SJ, Weaver DW, Maxwell NP, Bouwman DL. Surgical management of pseudomembranous colitis. American Surgery. 1988;54(6):329-32.

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Last updated: 2019-07-11 22:42