Neutropenic Enterocolitis: Case report and literature review

Typhlitis, is also known as neutropenic enterocolitis, affects the cecum and distal ileum. It was frequently encountered in pediatric patients who were undergoing treatment for leukemia. Nonetheless, it can affect adult patients, regardless of the cause of the immunosuppression. We report the case of a 20-year-old patient who was receiving chemotherapy for Osteosarcoma, who had a 6-day history of nausea and vomiting, fever sensation, diarrhea, and diffuse abdominal pain. Physical examination was relevant for hemodynamic instability, a distended and tender abdomen predominantly in the right iliac fossa. The laboratory workup showed severe neutropenia, thrombocytopenia, and electrolyte disturbances. The image studies evidenced edema of the ascending colon and cecum. Treatment was started with vasopressor support, correction of electrolyte alterations, blood cell and platelet transfusion, G-CSF, hydration, broad spectrum antibiotic therapy, initially with adequate clinical and laboratory response. After a few days, he presented lower gastrointestinal bleeding which was treated by conservative management. In conclusion, typhlitis must be suspected in every patient developing neutropenia as a reaction to chemotherapy and who also presents gastrointestinal symptoms, such as nausea, vomiting, diarrhea, and intense abdominal pain.

La tiflitis o también denominada enterocolitis neutropénica afecta el ciego e íleon distal. Fue descrita comúnmente en pacientes pediátricos sometidos a tratamiento para leucemia; sin embargo, puede afectar al paciente adulto independiente de la causa que origine la inmunosupresión. Presentamos el caso de un paciente de 20 años con antecedente de osteosarcoma, quien acude con tiempo de enfermedad de 6 días caracterizado por náuseas y vómitos, sensación de alza térmica, diarrea y dolor abdominal difuso. Al examen físico se encuentra hemodinámicamente inestable, abdomen distendido y se corrobora el dolor abdominal a predominio en fosa iliaca derecha. Los exámenes de laboratorio mostraron neutropenia severa, trombocitopenia y alteraciones hidroelectrolíticas. En los estudios de imágenes la TC evidenció edema de asas delgadas, así como edema de pared del colon ascendente y ciego. Se inició tratamiento con soporte vasopresor, corrección de alteraciones hidroelectrolíticas, transfusión de paquetes globulares y plaquetas, G-CSF, hidratación, terapia antibiótica de amplio espectro, inicialmente con adecuada respuesta clínica y laboratorial. Al cabo de unos días presentó hemorragia digestiva baja como complicación que fue tratada mediante manejo conservador. En conclusión, la tiflitis debe sospecharse en todo paciente que desarrolla neutropenia luego de quimioterapia y que presenta síntomas gastrointestinales como náuseas, vómitos, diarrea y dolor abdominal intenso. El manejo conservador, en pacientes con hemorragia digestiva y tiflitis, que involucra corrección de coagulopatía, transfusión de paquetes globulares e hidratación, puede ser el adecuado en pacientes que no cursan con inestabilidad hemodinámica y logran controlar el sangrado.

Enterocolitis neutropénica en el paciente oncológico pediátrico / Neutropenic enterocolitis in the pediatric cancer patient

Resumen La enterocolitis neutropénica (ECN) es una enfermedad heterogénea de foco digestivo, pero afectación sistémica, que corresponde a una condición clínica grave que amenaza la vida de pacientes inmunocomprometidos, particularmente oncológicos pediátricos. De patogenia aún poco definida y aunque de causa multifactorial, la ECN se asocia a los efectos citotóxicos de la quimioterapia empleada y se caracteriza por la triada clásica que incluye fiebre, neutropenia y dolor abdominal, donde la principal injuria se localiza en la mucosa intestinal, provocando su alteración como barrera y facilitando la invasión bacteriana intramural. La ECN constituye un reto diagnóstico para el equipo tratante, que requiere ser oportuno y contar con apoyo de un óptimo laboratorio general e imagenológico, para iniciar un completo manejo multidisciplinario en unidades y centros de alta complejidad. Se presenta una revisión actualizada del tema incorporando aspectos epidemiológicos, factores de riesgo, elementos de apoyo diagnóstico, consideraciones terapéuticas y medidas de prevención a fin de aportar en el conocimiento de esta patología, y reducir morbimortalidad en estos pacientes.

Abstract Neutropenic enterocolitis (NEC) is a heterogeneous disease of the gastrointestinal tract with systemic response, that corresponds to a severe and life-threatening clinical condition in immunocompromised patients, especially in childhood cancer. The pathologic features are poorly understood, although its multifactorial cause of NEC is well established and it is associated with the cytotoxic effects of the chemotherapy agents used and recognized by the classic triad of fever, neutropenia, and abdominal pain, secondary to gastrointestinal injuries that alters mucosal permeability and helps intramural bacterial invasion. NEC is truly a clinical challenge that requires an early diagnosis and a multidisciplinary approach including basic laboratory and imagological tests in high complexity centers. We present a current review, adding epidemiological aspects, risks factors, diagnostic support elements, therapeutic considerations, and preventive measures in order to provide knowledge of this disease and help to reduce morbidity and mortality associated with it.

Typhlitis in breast cancer patient using Docetaxel?based chemotherapy: case report / Tiflite em paciente com câncer de mama em uso de quimioterapia com Docetaxel: relato de caso

The authors report a case of neutropenic enterocolitis (typhlitis) secondary to the use of adju? vant chemotherapy for breast cancer treatment. A 46?year?old woman received the diagnosis of typhlitis and underwent a right hemicolectomy

Os autores relatam um caso raro de enterocolite neutropênica (tiflite) secundária ao uso de quimioterapia adjuvante para tratamento de câncer de mama. Uma mulher de 46 anos de idade foi diagnosticada com tiflite, sendo realizada hemicolectomia direita.

Management of acute colorectal diseases in febrile neutropenic patients / Tratamento das doenças colorretais agudas no paciente neutropênico febril

Patients with hematologic malignancies are susceptible to serious complications due to immunosuppression. Neutropenic-related infection is one of the major causes of morbidity and mortality in this group of diseases. Febrile neutropenia is a common complication of the hematologic neoplasm itself or chemotherapy, and has worse prognosis if prolonged (lasting more than 7 days) or severe (neutrophil count below 500 cells per µL). Among the usual sites of infection, we highlight the neutropenic enterocolitis and perianal infection as gastrointestinal complications of greater interest to the colorectal surgeon. Although most cases respond to conservative treatment, a portion of patients will need surgery for complete recovery. (AU)

Os pacientes com neoplasias hematológicas estão sujeitos a uma séria de complicações devido à imunossupressão. Infecção é umas das principais causas de morbidade e mortalidade nesse grupo de doenças. A neutropenia febril é uma complicação frequente da própria doença onco-hematológica ou da quimioterapia, e apresenta pior prognóstico se prolongada (duração acima de 7 dias) ou severa (contagem de neutrófilos inferior a 500 células por microlitro). Dentre os focos de infecção mais comuns destacamos a enterocolite neutropênica e a infecção perianal como complicações de maior interesse para o cirurgião colorretal. Apesar de grande parte dos casos apresentar boa resposta ao tratamento conservador, uma parcela de pacientes necessitará de cirurgia para completa recuperação.

A Case of Appendicitis with Liver Abscesses Developed during Allogeneic Hematopoietic Stem Cell Transplantation / 임상소아혈액종양

A 10-year-old boy with severe aplastic anemia was admitted for allogeneic hematopoietic stem cell transplantation. After conditioning chemotherapy using cyclophosphamide, fludarabine, and antithymocyte immunoglobulin, he presented with fever and abdominal pain on day 0 of stem cell transplantation. After diagnosis of acute appendicitis with minor perforation, appendectomy was performed just after cell infusion. A week after the procedure, he showed two huge liver abscesses in S4 and S6 segments. We used broad spectrum antibiotics along with antifungal agents. Percutaneous drainage was attempted, but no fluid was removed and no microorganisms were isolated. After 7 weeks of antibiotics and antifungal therapy, liver abscesses showed improvement. We report a case of successfully treated appendicitis with liver abscesses in a severely neutropenic patient during allogeneic hematopoietic stem cell transplantation.

A Case of Appendicitis with Liver Abscesses Developed during Allogeneic Hematopoietic Stem Cell Transplantation / 임상소아혈액종양

A 10-year-old boy with severe aplastic anemia was admitted for allogeneic hematopoietic stem cell transplantation. After conditioning chemotherapy using cyclophosphamide, fludarabine, and antithymocyte immunoglobulin, he presented with fever and abdominal pain on day 0 of stem cell transplantation. After diagnosis of acute appendicitis with minor perforation, appendectomy was performed just after cell infusion. A week after the procedure, he showed two huge liver abscesses in S4 and S6 segments. We used broad spectrum antibiotics along with antifungal agents. Percutaneous drainage was attempted, but no fluid was removed and no microorganisms were isolated. After 7 weeks of antibiotics and antifungal therapy, liver abscesses showed improvement. We report a case of successfully treated appendicitis with liver abscesses in a severely neutropenic patient during allogeneic hematopoietic stem cell transplantation.

A Case of Typhlitis Developed after Chemotherapy with Irinotecan and Cisplatin in a Patient with Small Cell Lung Carcinoma / 결핵및호흡기질환

Typhlitis is a necrotizing colitis that usually occurs in neutropenic patients and develops most often in patients with hematologic malignancies such as leukemia and lymphoma. Typhlitis may proceed to bowel perforation, peritonitis and sepsis, which requires immediate treatment. Irinotecan is a semisynthetic analogue of the natural alkaloid camptothecin which prevents DNA from unwinding by inhibition of topoisomerase I. It is mainly used in colon cancer and small cell lung carcinoma (SCLC), of which the most common adverse effects are gastrointestinal toxicities. To the best of our knowledge, no case of typhlitis after chemotherapy with a standard dose of irinotecan in a solid tumor has been reported in the literature. We, herein, report the first case of typhlitis developed after chemotherapy combining irinotecan and cisplatin in a patient with SCLC.

Outcome of typhlitis in children with cancer / 소아과

PURPOSE: Neutropenic enterocolitis is an acute, life-threatening inflammation of the small and large bowel, often seen in children with malignancies during periods of prolonged or severe neutropenia. The optimal management for typhlitis in pediatric oncology patients has been debateful between operative and nonoperative approaches. The purpose of this study was to review the outcome of medical management of patients who were diagnosed as typhlitis. METHODS: The records of 207 pediatric cancer patients who were diagnosed and treated at the pediatric department of Yeungnam University Hospital for cancer between August, 2002 and July, 2007 were reviewed. RESULTS: Among 207 patients, 12 (5.7%) children aged 9 to 14 years, were diagnosed clinically to have typhlitis. Clinical symptoms and signs of patients were fever, abdominal pain and tenderness, diarrhea, vomiting and rebound tenderness. Bowel-wall thickening (> 4mm) was seen on CT or ultrasonography. All patients were treated with antibiotics combinations of teicoplanin, carbapenem, aminoglycoside, or other third generation cephalosporin and metronidazole or clindamycin. Eight patients were treated with additional antifungal agents. Other supportive management included bowel rest, total parenteral nutrition, and G-CSF administration. All patients recovered completely and did not need any surgical management. CONCLUSION: Early diagnosis and aggressive supportive treatment appears to be important for complete recovery and survival of typhlitis.

Typhlitis due to propylthiouracil in a patient with hyperthyroidism / 대한내과학회지

Typhlitis is one of the most ominous complications in immunocompromised patients. Neutropenic enterocolitis or typhlitis is a clinical syndrome characterized by fever, diarrhea and abdominal pain that occurs in neutropenic patients. It has been reported as a complication of childhood leukemia, but is now known to occur in adults with solid malignancies, acquired immunodeficiency syndrome (AIDS) or bone marrow transplantation (BMT). The association of typhlitis and propylthiouracil has not been previously reported. We report a case of a 42-year-old female patient with typhlitis due to propylthiouracil patient with hyperthyroidism.

Neutropenic Enterocolitis in Acute Myelogenous Leukemia

Neutropenic enterocolitis is an acute life-threatening, necrotizing inflammation of cecum and terminal ileum often seen in leukemia and lymphoma during periods of prolonged or severe neutropenia. It has been also referred to as necrotizing enterocolitis, ileocecal syndrome, or typhlitis (from the Greek word typhlon meaning cecum). The pathophysiology of the neutropenic enterocolitis is unknown but is believed to be multifactorial. The clinical symptoms of neutropenic enterocolitis are nonspecific including fever, abdominal pain (often right lower quadrant), abdominal distension, diarrhea, bloody stools, nausea, and vomiting. So acute appendicitis is should be included in the differential diagnosis. The early signs and symptoms are nonspecific and it may rapidly lead to intestinal perforation. The definite management of neutropenic enterocolitis is contrversial. but the prognosis is likely to be good with early diagnosis and proper management. We report one case of neutropenic enterocolitis in acute myelogenous leukemia with literature review.

Right Lower Quadrant Pain in Patients with Acute Myeloid Leukemia

PURPOSE: Acute appendicitis and typhlitis are difficult problems in acute myeloid leukemia (AML) patients. Whereas the treatment of typhlitis is primarily conservative, acute appendicitis is managed by surgery. The difficulty lies in distinguishing between the two becauae they both present similar conditions, and before surgery or autopsy, differentiation of these disease is nearly impossible. Careful evaluation is necessary before considering surgical treatment. In order to determinate proper treatment, we have reviewed our experiences with the right lower quadrant (RLQ) abdominal pain in patients with AML. METHODS: From July 1990 to December 2001, at St. Mary's hospital, Seoul, Korea, the records of AML patients that were consulted to the surgical department for RLQ abdominal pain were reviewed. Thirty patients were consulted and 12 out of the 30 patients underwent surgery. RESULTS: The average age of the patients who underwent operation was 33.9, with 9 males and 3 females. Six patients were in complete remission, and the other 6 were in the active state. RLQ pain was the first symptom of AML in four patients. All 12 patients had RLQ pain and 10 had rebound tenderness. In three patients, the white blood cell (WBC) count was less than 1, 000/mm3. Appendectomy was performed in five patients, appendectomy with drainage was performed in five, and laparoscopic appendectomy was performed in two patients. The final diagnosis was periappendicial abscess in four cases, leukemic cell infiltration in three cases, adenocarcinoma in one case, and typhlitis in three patients. Four patients developed wound infection and one patient died due to sepsis 7 days after the operation. For the patients who were treated medically, the average age was 36, with 11 males and 7 females. Seven patients were in the active state, three patients were in CR, four patients were in the refractory state, and two patients were in relapse. Six patients died within one month because of sepsis or pneumonia. CONCLUSION: Surgery is safe and is the sole method that can improve the survival rate in patients with AML and RLQ abdominal pain. Furthermore, complications related to surgery may be reduced through the laparoscopic surgery.

A case of typhlitis developed after anticancer chemotherapy in a patient with solid tumor / 대한내과학회지

Typhlitis is a necrotizing enterocolitis of the cecum, ascending colon and terminal ileum. Typhlits has been reported in the severely neutropenic patients and likely results from a combination of neutropenia and defects in the bowel mucosa related to cytotoxic chemotherapy. This disease is most common in patients with leukemia who have undergone intensive myeloablative chemotherapy. Presumptive diagnostic criteria for typhlitis include fever, abdominal pain and tenderness, and radiologic evidence of right-sided colonic inflammation in patients with neutropenia. Recently, this disease is also reported in patients with solid tumor due to increasing challenges of high dose chemotherapy. We report a case of typhlitis developed in the circumstance of neutropenia induced by chemotherapy in a patient with malignant testicular tumor.

Exploration of clinical diagnosis and treatment for acute typhlitis / 临床外科杂志

Objective To improve the understanding of acute typhlitis.Methods all 5 cases of acute typhlitis from February 1999 to August 2001 were reviewed,5 cases were preoperatively misdiagnosed as acute appendicitis and subsequently performed emergency operations.Moreover,misdiagnosis was made intraoperatively as tumor in 2 cases,Crohn disease in 2 cases and diverticulitis in 1 case.Right hemicolectomy was performed in 4 cases;resection of necrotic mass and ileostomy was performed in 1 case.Results The pathologic change was acute non-specific inflammation of cecum in 5 cases.All cases recovered uneventfully.They are in good condition during the follow-up range 4 to 30 months.Conclusions The clinical manifestation of typhlitis was nonspecific.It was extremely difficult to diagnose preoperatively.Inflammatory mass of external lateral wall of cecum was characteristic finding of typhlitis during laparatomy.It is difficult to differentiate from tumor or Crohn disease at intraoperation.Right hemicolectomy was satisfactorily recommended.

Two Cases of Perforated Typhlitis in Acute Lymphocytic Leukemia

chemotherapy. Serial ultra sonograms and CT scans demonstrated irregular thickening of the cecal wall (6-15mm in thickness) and subsequent small perforation of the posterior wall of the cecum with thick-walled localized abscess. She has recovered completely after aggressive medical management. We learned two lessons from our experience treating these patients:1) early diagnosis provided by a high index of suspicion and the use of ultra sonogram or CT scan is essential. And 2) although perforation is one of the surgical indications for the treatment of typhlitis, it is possible to manage the perforation nonoperatively in selected cases with localized abscess.The authors, over the last 6 months, have treated 2 patients with perforated typhlitis complicating acute lymphocytic leukemia (ALL) with good outcome. The first patient was a 13-year-old male who developed intermittent high fever, abdominal pain, abdominal distention and diarrhea during the course of maintenance chemotherapy. The peripheral leukocyte ranged from 230-470/mm3. Serial ultra sonograms and CT scans demonstrated irregular thickening of the cecal and ascending colonic walls and subsequent ragged perforation of the posterior wall of the cecum. He survived after treatment by right hemicolectomy and aggressive supportive measures. The patient case was a 3 year-old female who developed intermittent high fever, right lower abdominal pain, a mass, and watery diarrhea during the course of maintenance.

A Case of Acute Typhlitis Complicating Drug-induced Agranulocytosis / 대한내과학회지

Increasingly aggressive chemotherapy regimens, advances in transplantation technology, and the acquired immunodeficiency syndrome have resulted in a growing number of immunocompromised patients. Infections are a major cause of morbidity and mortality in this population. One of the most ominous complications is the development of typhlitis in this immunocompromised patients. Treatment of this process is controversial, and no consensus has emerged. We report a case of typhlitis who complicated agranulocytosis after exposure to drugs to treat "flu" like illness and recovered completely after two operations of appendectomy and ileocolectomy. Reviewing articles and this case, the favorable outcome seemed to be related to following three factors recognition of the acute surgical abdomen by abdominal CT scan, a prompt return of normal circulating white cells by the use of Granulocyte Colony Stimulating Factor and discontinuation of causative drugs, and an appropriately timed surgical intervention.

Four Cases of Typhlitis, Developed in Neutropenic State and Treated with Medical Conservative Management / 대한암학회지

Typhlitis is a life threatening necrotizing enterocolitis of the cecum, ascending colon and terminal ileum seen in severely neutropenic patients, however its pathogenesis is not identified up to this time.The incidence of typhlitis in leukemic patient is 10~12%, estimated by postmortem examination, and 46% in induction chemotherapy of leukemia. Recently, entity incidence is more high due to increasing challenges to high dose chemotherapy in solid tumors.We experienced four cases of typhlitis, one was developed in the circumstance of neutropenia induced by induction chemotherapy for acute myelocytic leukemia and others in neutropnia due to primary diseases without chemotherapy, ig, chronic myelocytic leukemia, acute lymphocytic leukemia, myelodysplastic syndrome.All cases were treated with high dose broad spectrum antibiotics in early phase of disease and its outcome was good, so that, early diagnosis of typhlitis is essential, then prompt treatment with high dose antibiotics and intravenous fluid before onset of transmural necrosis is associated with lower morbidity and mortality than surgical resection.